Science in Society Review - Spring 2012 by The Triple Helix at UChicago

ASU · Berkeley · Brown · Cambridge · CMU · Cornell · Dartmouth · Georgetown · Harvard · JHU · Oxford Northwestern · NUS · Penn · UChicago · UCLA · UNC Chapel Hill · University of Melbourne · UCSD · Yale Spring 2012 | University of Chicago

ISSN 2164-4314

More Important than Money: Sleep The Alien Ceres: Promises and Precautions of Modern Agriculture Acupuncture: A Needling Medical Mystery The Criminal Mind

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EXECUTIVE MANAGEMENT TEAM

BOARD OF DIRECTORS

Chief Executive Officer Jennifer Ong

Chairman Kevin Hwang

Chief of Global Affairs Jacob Parzen

Vice Chairman Erwin Wang

Executive Editor-In-Chief Dhruba Banerjee

Secretary Melissa Matarese

Chief Production Officer Darwin Chan

Alumni Chair Joel Gabre

Executive Director, E-Publishing Zain Pasha

Finance Chair Kalil Abdullah

Executive Director, Internal Affairs Jennifer Yang Executive Director, Science Policy Faisal Rahimi Chief Marketing Officer Kyle Wemple Chief Financial Officer Robert Qi Chief Operating Officer, Europe Francesca Day Chief Operating Officer, Australia Madeleine Chan Chief Operating Officer, North America Mridula Nadamuni Chief Operating Officer, Asia Chin You Chuen INTERNATIONAL STAFF Senior Literary Editors Titas Banerjee Jefferson Chen Michael Graw Vicky Phan Harrison Specht Linda Xia Senior Production Editors Luna Chen, Cornell Jasmine Chuang, Cornell Hyo Jin Jessica Lee, Cornell Andrew Kam, UChicago Ai Ming Chow, Melbourne Cassie Yeh, Berkeley Elizabeth Seaman, Georgetown Senior E-Publishing Editors Venkat Boddapati Benjamin Dauber Jae Kwan Jang

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Board Members Manisha Bhattacharya Julia Piper James Shepherd TRIPLE HELIX CHAPTERS North America Chapters Arizona State University Brown University Carnegie Mellon University Cornell University Georgetown University Georgia Institute of Technology The Harker School Harvard University John Hopkins University Oxford University University of California, Berkeley University of California, San Diego University of Chicago Yale University Europe Chapters Cambridge University Asia Chapters National University of Singapore Australia Chapter University of Melbourne

THE TRIPLE HELIX A global forum for science in society

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!

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TABLE OF CONTENTS The Alien Ceres

Acupuncture

Modern agriculture

A needling mdical mystery

The Criminal Mind How free is free will?

More Important than Money: Sleep

UCHICAGO UC CH C HI

Cover Article Eric Bai, Brown

Local Articles 7

The Amazing Utility of Junk DNA - Versatility of Scientific Facts

Azfar Basunia

“If our brains were so simple…” Minding the Gap

The Alien Ceres: Promises and Precautions of Modern Agriculture

Of Resources and Trust: The Battle for STD Screening in Low-income North America

Top and Bottom or Truth and Beauty?

Healthcare Reforms: The Eagle and the Dragon

Frank Qian

Acupuncture: A Needling Medical Mystery

Talia Retter

The Criminal Mind

Bill Dague Niloufar Hafizi Sami Ismail

Tyler Lutz

Margaret Sivit

International Features 33

The Bright Side of the Black Market: The Case of Street Suboxone

Sandeep Manel Nayak, Brown

Reading Reinvented: How Computers and the Internet are Influencing our Society

Latha Panchap, Cornell

The Chemistry of Medicinal Plants: Phytochemicals as Novel Chemotherapeautic & Biomedical Interventions

Spenser Reed, Cornell

Cover Design courtesy of Eric Bai ‘15 and Maja Czemier-Wolonciej ‘13 from Brown University. Book 1.indb 1

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INSIDE TTH

Message from the Executive Board STAFF AT UCHICAGO Co-Presidents Benjamin Dauber Tae Yeon Kim Director of Marketing Luciana Steinert Associate Director of Marketing Alexi McCammond Editor-in-Chief Jonathan Gutman Managing Editors Benjamin Dauber Lily Gabaree Nori Lu Navtej Singh Luciana Steinert E-Publishing Editor-in-Chief Edgar Pal

Dear Reader, It is with great excitement that we bring to you the 2012 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 an interdisciplinary 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. This print cycle was unique: for the first time in our chapterâ&#x20AC;&#x2122;s history, we published articles written by those students who conducted original research projects. We are proud to encourage our future leaders in their 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. Benjamin Dauber Co-President

Tae Yeon Kim Co-President

Jonathan Gutman Editor-in-Chief

E-Publishing Managing Editors Andrew Kam Gregor Siegmund Melissa Cheng Senior Production Editor Andrew Kam Production Editors Christina Chan Wujun Ke Shelby Winans Writers Azfar Basunia Frank Qian Niloufar Hafizi Tyler Lutz Talia Retter Sami Ismail Maggie Sivit Bill Dague Associate Editors Maya Lim Gala Ades-Laurent Melissa Cheng Austen Smith Tinley Melvin Han Li Jack Bliamptis Jonathan Perez Lakshmi Sundaresan Faculty Review Board Jason Bridges Jeff Bridges Kathleen Cagney Anne Henly Nita K. Lee Manyuan Long Robert J. Richards Chun-Su Yuan Events Coordinator Catherine Castro Rachel Kulikoff Tim Rudnicki

Local News We are having a successful year here at the University of Chicago. In addition to this print journal, we also publish student articles on the Triple Helix Online, a publication rated among the top five science policy blogs on the web today by OnlineCollege.org. Electronic articles are read by over 300 unique visitors to our website per day. We have expanded our online division through new recruiting and marketing efforts. In terms of events, since the end of Autumn Quarter, the Triple Helix at the University of Chicago has been experimenting with a new structure for the Events Division. Instead of a single Science Policy Director, we now have a three-person Events Committee. Our Event Coordinators have worked closely with the Marketing and Production Divisions to successfully advertise our events. This quarter, we hosted a lecture by Lainie Ross, MD, PhD on the ethical and policy issues in organ transplantation. The audience was highly engaged and brought up many questions at the end of the lecture. Currently, we are collaborating with several other student organizations to coordinate a panel on racial health disparities, and hope to continue our community outreach efforts by bringing high school students to campus for lab tours. Our Marketing and Production Divisions have also expanded this year. We are proud to encourage our future leaders in their rigorous exploration for the key issues in society today.

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INSIDE TTH

Message from the CEO In October 2004, a Cornell University freshman had the idea of putting together a student organization that would look beyond the intellectual appeal of science and make critical connections between science and its relevance to other disciplines that shape our society. The Science in Society Review, the first product of The Triple Helix, was published in 2005, and the concept became so popular that over the next two years, the organization would expand to fifteen other US chapters and into three international regions. We are constantly striving to be better. This was the year in which recent graduates played a more active role within the organization, thus building a foundation of collaboration and mentorship that we hope to maintain in the years to come. This was the year that we revamped our logo, created a new international website and standardized our international message. This was the year we instituted official social media outlets, shared our progress via monthly newsletters, reached out to local communities, and experienced ground-breaking attendance at both our annual conference and local science policy events. This was the year of new programs with the establishment of The Quanta (TTH@ASU), e-mentoring, podcasts, extra features, and alumni networks. And this year, we were proud to welcome UC Davis, Duke University, and the University of Oxford to our ever-growing list of TTH chapters. In the last eight years, we’ve grown a tremendous amount. Yet what makes The Triple Helix so unique isn’t our Science in Society Review, our e-publishing division, our science policy podcasts, or even our extensive chapters, but our people. The Triple Helix would not be successful without the hard work, passion, and dedication of our writers, editors, leaders, and international team. So to everyone who has been involved in any capacity in this past year – from our international team, chapter leaders, editors, writers, and yes, our readers – thank you. Thank you for your time and effort. Without you, we would not have been able to come this far; and yet, still have the potential to accomplish so much more. Cheers, Jennifer Ong Chief Executive Officer

Message from the EEiC and CPO

Did you have strong opinions about any of the articles in this issue? Interested in giving feedback to the writers or editors? Engage in a dialogue through a letter to the editor. Email eeic@thetriplehelix.org for more information. Your letter may appear in the next issue of the Science in Society Review!

Sleep deprivation is no stranger to most college-age students. Pulling all-nighters to finish problem sets and papers seems worthwhile because we value our academic achievement over the seemingly trivial rest and relaxation of dream land. But in the Spring 2012 edition of the Science in Society Review, Eric Bai of Brown University, questions this assumption in our cover story “More Important than Money: Sleep” Welcome to the biannual journal of The Triple Helix! Whether you are a loyal reader or you have just picked this up for the first time, inside you will find a unique forum for science, society, and law. We feature interdisciplinary articles that examine the nexus of science, society, and law to make sense of current events, global problems, and new discoveries and policies. All of our work is done by undergraduates. This publication cycle, writers and editors from ten chapter universities have contributed to this journal! Their tireless work has been complemented at the International level by the International Editorial Board, comprised of hardworking Senior Literary Editors. Multiple teams located across the country have worked together to layout these journals. Much thanks to the senior production editors at Cornell, Berkeley, UChicago, and Georgetown, who have been leading these teams to complete the task of delivering the journal in print to your hands. We hope you enjoy reading through this edition of the Science in Society Review. If you are intrigued by these articles, we hope you will engage with a dialogue with the writer by sending a Letter to the Editor or joining The Triple Helix. Sincerely, Dhruba Banerjee and Darwin Chan Executive Editor-in-Chief and Chief Production Officer

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BROWN

More Important than Money: Sleep Eric Bai

leary-eyed vision and lack of concentration, the physical realities of sleep deprivation are unmistakable. With an estimated one third (50 to 70 million) of adults in the United States reporting insufficient sleep and a purported $15 to $92 billion in annual economic losses as a result of sleep-induced negligence, inquiry into social assumptions regarding sleep becomes crucial [1]. While our time-honored notion of the man “early to bed and early to rise” as one who is “healthy, wealthy, and wise” remains firmly ingrained in our social consciousness, the traditional monophasic mode of sleep (sleeping at night) is an anachronism in a world where night no longer signals the end of the productive workday. Understanding the impact of valuing efficiency over health is possible only when we consider tailoring work to the worker rather than the worker to his work. The Development of Shift Work Thomas Edison’s commercialization of the light bulb in the late nineteenth century marks the substitution of human labor with machine labor, when work could continue unabated day or night [2]. Our modern day glorification of the sleepless, overambitious employee as the epitome of the efficiency continues this trend [3]. Corporate executives schedule late-night dinners and earlymorning receptions in a bid to conduct as much business as possible in one day. Investment bankers wake up to the ringing of their alarm clocks at 2:30AM to track the opening of the DOW [3]. Still, others elsewhere work to fuel the lifeblood of a society built on the here and now. Packers, pilots, and truck drivers labor throughout the night to ensure timely delivery of packages. Airplane mechanics and highway repair crews work at night to avoid the bustle of daytime traffic. Doctors and nurses operate on-call to ensure the delivery of health care to those critically ill. As we grow to value Gross Domestic Product over Human Development Index, a combined measure of life expectancy, educational attainment, and income, we focus increasingly on perceived quantity of output over actual quality of work. We measure success by number of deals closed, number of packages delivered, number of miles travelled, number of patients seen—so much so that we forget to consider the productive possibilities of a work schedule tailored to respect our innate need for rest. The growing

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mechanization of industry in the mid-twentieth century resulted in an “economic democracy planned by all members of the industrial organization,” but failed to consider the “’neurobiological cost’” of operating on borrowed time [4,5]. Working in lieu of sleep is not without its consequences. What is Sleep and What is a Lack of It? Harvard Medical School Professor Charles Czeisler divides the need for sleep into four factors: (1) an innate drive for sleep, (2) total amount of sleep over the past several days, (3) perception of time of day, and (4) “sleep inertia,” the drowsiness experienced upon waking up [3]. Sleep is not only the product of interaction between these four factors, but also the result of variations within each factor: caffeine or exercise can temporarily reduce innate drive for sleep; sudden changes in work scheduling can unexpectedly lower total amount of sleep; an unusually dark work environment may skew perception of time of day [5]. Chronic sleep loss is difficult to treat because of the considerable variability of factors contributing to the diagnosis. Despite these difficulties, when we consider that

Reproduced from [13]

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BROWN one out of every three Americans experiences difficulty sleeping, this issue becomes impossible to ignore [2]. Although sleep deprivation is prevalent, current shift schedules only compound this problem through their dismissal of sleep as a requirement for productive work. Sleep-deprived workers are not only a workplace hazard, but also a burden on the healthcare system. Workers short of sleep cost employers on average 8.8 days of wasted wages a year due to sick leave and lower efficiency and accrue $14 billion in direct healthcare expenses [6]. With the prevalence of shift work today, these hidden costs represent a widely-distributed threat manifested in many forms. In hospitals, sleep-deprived healthcare professionals make 36% more life-threatening medical errors and five times as many serious diagnostic errors as their well-rested counterparts [6]. On roads, drowsy drivers account for 20% of all motor vehicle accidents and 8,000 deaths annually [3]. Preventable accidents stemming from a lack of sleep litter the annals of local and national media: the Exxon Valdez oil spill in Prince William Sound, the 1988 Aloha Airlines accident, or the Joubert tragedy in Beaumont, Texas [2,3]. Taken together, it is unsurprising that a nine-year longitudinal study commissioned by the National Commission on Sleep Disorders Research found a 70% higher mortality rate for those chronically deprived of sleep [2]. Though the cost of foregoing sleep is substantial, it is too often ignored.

We measure success by number of deals closed, number of packages delivered, number of miles travelled, number of patients seen— so much so that we forget to consider the productive possibilities of a work schedule tailored to respect our innate need for rest

A Different Mode of Sleep Our symptomatic rather than holistic approach to illness seeks to conclusively address sleep loss with a pill. Despite the risk of addiction, Ambien remains the de facto standard for treatment of insomnia [3]. This methodology erroneously attempts to distill an intricate social phenomenon into a convenient, individuallypackaged solution. It would be more productive to examine the viability of napping regimens and alternative modes of sleep distinct from the traditionally monophasic. Although monophasic sleep © 2012, The Triple Helix, Inc. All rights reserved.

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enjoys a high degree of acceptance in our conventional mode of work, it is largely a social construct rather than a natural human tendency [7]. When deprived of external stimuli and sources of distraction, human subjects exhibit a napping schedule that closely approximates the four-hour polyphasic sleep cycles of newborn infants [7]. In societies with a more casual sociological order, or the less-structured lifestyle of the elderly, a biphasic pattern of sleep emerges [7]. In the course of physiological development, sleep begins as polyphasic, and, largely due to the constraints of school and work, gradually progresses towards the biphasic sleep of young children and eventually the monophasic sleep of adults [7]. Rethinking Shift Work Design To maximize productive gains, industry increasingly relies on twelve-hour rather than eight-hour shifts [10]. Under this system, employees work longer hours and have less time to rest, exacerbating existing sleep deficiencies. The solution may be surprisingly simple: permission to nap. For the 15% of U.S. and Canadian companies that permit napping, the incidence of accidents and lapses in judgment has decreased by 30% [7]. Otherwise, altering scheduling systems to minimize sleep cycle disruption can also reduce issues stemming from extension of shifts [8]. Novel work schematics have already been successfully tested in a wide variety of settings. The Italian Air Force adopted a part-monophasic, part-polyphasic sleep schedule alternating daily which resulted in minimal reduction of attentiveness and performance [9]. This case demonstrates the feasibility of rotating sleep patterns within a single shift. A later Finnish study concluded that allowing for a twelve-hour period for sleep after moderate sleep deprivation was an effective means of restoring alertness compared to only a short rest pause and light exercise [10]. This scenario adopts a more traditional alternation between periods of activity and rest to combat sleep deprivation. Selection of an appropriate shift schedule depends on the set of conditions at hand, but, regardless of type, schedules must recognize sleep deprivation as a critical barrier to efficient operation in order to maximize productivity and well-being. Whether fixed or rotating, straight or oscillating, primary or staggered, implementing more desirable shift schedules preserves total amount of hours worked while dramatically increasing quality of time off [2]. At a Sandoz chemical plant, a new schedule deemed the “double long change” was so desirable that electricians and maintenance workers volunteered to rotate shifts round-the-clock. Total work time with this staggered shift remained constant, but work was scheduled more cohesively, allowing for greater predictability and improved overall well-being [9]. Similarly, shift workers at Portland General Electric’s Beacher, Oregon plant voluntarily gave up pay to switch to the same schedule as the nearby Boardman plant, which offered thirty-one weekends off and up to ten weeks of vacation per year [9]. Enhanced efficiency during working hours at the Boardman plant allowed for greater opportunity to rest and also reduced total commuting time all without impacting business operations [11]. These optimized shift assignments prevent the buildup of sleep debt [9], guaranteeing alertness and preventing impaired performance due to fatigue [12]. Work schedules with fewer consecutive shifts and more frequent days off do not compromise efficiency. They do, however, decrease cost of operations by reducing emphasis on premium pay as a THE TRIPLE HELIX Spring 2012 5 3/29/2012 7:56:52 PM

BROWN means to attract an intrinsically motivated labor force [9].

Reproduced from [14]

Employers vs. Employees: A Conclusion When we consider the exhausted employee overseeing the safety gauges at a nuclear power plant or the overnight guard monitoring inmates in their cells, we must also take into account the demand for services generated by the growing importance of the night shift. While the economic importance of shift work renders it financially and productively indispensable, the enormous human cost of such work can be minimized by appropriate scheduling and collaboration between the worker and his organization, the manager and his company, and the doctor and his hospital [12]. While employers move to increase cohesiveness of off-time, employees must also learn to prioritize rest. In this sense, sleep deprivation is a personal, biological, cultural and economic phenomenon. While a personal

Implementing more desirable shift schedules preserves total amount of hours worked while dramatically increasing quality of time off

issue, inadequate sleep stems from biological and cultural factors and adversely affects performance at the workplace. Only when we begin to realize that the emergent effect of sleep on well-being is greater than number of hours a night can we achieve the “freedom in industry” touted by early industrialists in our modern-day postindustrial society [4]. Eric Bai is a freshman at Brown University considering a double concentration in Biochemistry and Sociology.

References 1. Sivertsen B, Lallukka T, Salo P. The economic burden of insomnia at the workplace: An opportunity and time or intervention? SLEEP 2011;34(9):1151-1152. 2. Oexman RD, Knotts TL, Koch JL. Working while the world sleeps: A consideration of sleep and shift work design. Employee Responsibilities and Rights Journal 2002;14(4):145-157. 3. Fryer B. Sleep deficit: The performance killer. Harvard Business Review 2006;84(10):5359. 4. Weiss H. Human relations in industry. American J Economics & Sociology 1949;8(3):287-297. 5. Van Dongen HPA, Maislin G, Mullington JM, Dinges DF. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. SLEEP 2003;2:117126. 6. The Center for Medicine in the Public Interest. Waking up to the insomnia crisis: How insomnia is costing America more than $42 billion a year and what we can do about it. [serial on the Internet]. 2009 [cited 2011 Oct 15]. Available from: http://www.cmpi.org/ uploads/File/Insomnia-paper-5.15.09_final.pdf

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7. Zulley J, Bailer J. Polyphasic sleep/wake patterns and their significance to vigilance. In: Nachreiner F, ed. Studies in industrial and organization psychology. Frankfurt: Verlag Peter Lang, 1988:167-80. 8. Takahashi M. The role of prescribed napping in sleep medicine. Sleep Medicine Reviews 2003;7(3):227-235. 9. Coleman RM. Cost effective shift schedules enhance utility operations. Power Engineering 1995;99(2):27==. 10. Porcu S, Casagrande M, Ferrara M, Bellatreccia A. Sleep and alertness during alternating monophasic and polyphasic rest-activity cycles. International J Neuroscience 1998;95(1-2):43-50. 11. Sallinen M, Holm A, Hiltunen JL, Hirvonen K, Harma M, Koskelo J et al. Recovery of cognitive performance from sleep debt: Do a short rest pause and a single recovery night help? Chronobiology International 2008;25(2-3):279-296. 12. Baulk SD, Fletcher A, Kandelaars K, Dawson D, Roach Gd. A field study of sleep and fatigue in a regular rotating 12-h shift system. Applied Ergonomics 2009;40(4):694-698. 13. http://health.mo.gov/living/families/wic/wicfamilies/education/img/babysleeping.jpg 14. http://www.nlm.nih.gov/hmd/goya/images/sueno.jpg

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UCHICAGO

Nanomedicine and the Potential for Nanofibers to Regenerate Blood Vessels Azfar Basunia

paramount advancement in biological sciences was made when scientists Dr. Craig Venter and other colleagues from the Human Genome Project published the entire sequence of the human genome on February 2001 [1]. One of the largest single investigative projects in the history of science, the human genome project signified more than a decade of international collaborative from numerous universities and research institutions across America, Europe, and Asia. After the completion of the project, scientists worldwide were awestruck by the results. The difference between the predicted number of human genes (100,000) and the actual number of mapped genes (25,000) was more than 100 fold! The enormous size of the human genome (3.3 billion base-pairs) and the diversity of proteins in the human body all pointed to about 2 million genes. What truly astonished the scientists was the overall composition of the human genome – only about 1.4% of the DNA coded for functional proteins. The sheer number of noncoding DNA, the other 98.6% of the genome perplexed scientists around the globe. In the 1970s, the term “junk DNA” was coined to label the noncoding DNA that did not transcribe proteins [2]. Francis Crick, codiscoverer of the structure of DNA and Nobel Laureate, supported the view that junk DNA was useless and stated that such junk DNA has little specificity and conveys little or no selective advantage for the organism [2]. However, even before the human genome was fully sequenced, a Polish biologist Wojtek Makaloski, challenged Crick’s idea of junk DNA and published how a specific repetitive DNA sequences (called Alu elements) can cause protein diversity [3]. Since then, with improved technology and techniques of the 21st century, scientists uncovered important biological functions associated with the term “junk DNA,” obsoleting the term in modern biology. So how did scientists resolve the presence of large chunks of junk DNA in the human genome? Researchers began to think outside the “central dogma of biology” – first articulated by © 2012, The Triple Helix, Inc. All rights reserved.

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Francis Crick himself in 1958 [4]. The central dogma states that proteins are the functional units of biological mechanisms while DNA codes for the proteins and RNA mediates the production of proteins. Research by Thomas Cech and Sidney Altman in the early 1980s attempted to disprove the central dogma by showing additional enzymatic functions of non-coding RNA (i.e RNA molecules that are not translated into proteins), for which they won the Nobel Prize in 1989 [5, 6]. Other scientists attempted to seek out similar phenomenon demonstrated by Cech and Altman – could such “junk DNA” and non-coding RNA behold functional properties in their native states without being translated into proteins? Their discoveries elegantly answered why non-coding DNA, comprising of 98% of the human genome, does not code for proteins but is still useful. Non-coding DNA serves two critical functions in cell maintenance: they act as gene enhancers and telomeres. Non-coding DNA regulates gene transcription – production of protein-coding RNA from DNA – without the aid of proteins or RNA. Non-coding DNA sequences have the ability to manipulate and regulate gene functions over long distances, measured by base-pairs or nucleotide sequences, Reproduced from [16] by physically twisting, rotating or turning over to bring “special regions” of DNA together. These “special regions” – gene enhancers or regulators – interact to affect gene expression [7]. Terminal non-coding DNA in chromosomes serves as telomeres. Telomeres protect DNA deterioration due to inherent mechanistic flaws of linear DNA replication [8]. Recent research has correlated telomere degradation to aging [9]. Since such findings, several ongoing research projects around the world are exploring the anti-aging effects of telomere preservation. Hence, what scientists previously classified as “junk DNA” ironically has important functions in the maintenance of the overall well being of the cell and the organism. Functions of non-coding RNA are just as versatile as that of non-coding DNA. Non-coding RNA can also act to enhance/ THE TRIPLE HELIX Spring 2012 7 3/29/2012 7:56:53 PM

CMU UCHICAGO repress transcription of protein coding DNA. In the recent years, another crucial biological phenomenon – RNAi – has been attributed to non-coding RNA. RNA interference (RNAi) uses non-coding RNA to mediate the expression of proteins. Through RNAi, cells can control the expression of endogenous genes. More importantly, cells can block the expression of viral proteins in a viral infection [11]. Cells that incorporate parts of viral genes in their genome as a result of previous infections produce special non-coding RNA to inhibit viral protein production and fight viral infections [11]. In recent years, many investigators are exploring the possibilities of using RNAi to inhibit cancer growth and repress cancer causing genes [12]. In the last decade, over 75,000 miRNA (a type of RNA that exhibits RNAi) have been discovered in the human genome [10].While the discovery of novel miRNA is still ongoing, all such miRNA were previously considered “junk DNA.”

The sheer number of noncoding DNA, the other 98.6% of the genome, perplexed scientists around the globe

Despite the significant therapeutic potential of RNAi, recently discovered techniques that seem to work in theory are meeting considerable roadblocks in medical experiments. RNAi therapy – a method of inhibiting malignant genes to treat diseases – gained widespread popularity among the scientific community as a possible avenue for gene and cancer therapy. However, in one study, high death rates of mice suffering from liver diseases were noted when RNAi treatment was administered [13]. Furthermore, conventional gene therapy – insertion of functional genes into defective cells – has met

several road blocks in the U.S. after the reported deaths of participants in clinical trials [14]. Problems arise when the inserted genes or RNA can themselves disrupt normal cellular process or mis-target normal cells. The viral vectors used to deliver the therapeutic agents can also create complications – cells may also respond adversely to the viral vectors, and reject the treatment altogether. All of these problems pose serious questions and doubts on the applicability of RNAi based treatments and gene therapy. The utility of junk DNA demonstrates the notion that scientific “facts” and theories are versatile, refutable, and replaceable. Scientific research does not establish “statements of absolute truth”; rather the aim of research is to make claims via hypothesis testing with varying degrees of confidence [15]. Degrees of confidence state the probability that a certain observation is occurring due to an underlying effect (which the hypothesis lays out and the experiment tests for) not random chance [15]. The term “junk-DNA” is a misnomer for non-coding DNA, which in fact does serve diverse functions that were unknown when the term was coined. Similarly, the central dogma of molecular biology famously coined by Francis Crick no longer holds as a working scientific theory. Newer and more accurate scientific instruments provide scientists with a new angle to evaluate scientific claims; those that do not withstand these newer tests are falsified. Hence, these so called scientific facts represent our observations of a scientific phenomenon through the lens of contemporary scientific instruments and experimental procedures. The notion of so-called junk DNA existed because scientists did not have the proper tools or procedures to evaluate the function of non-translated DNA. This evolution of scientific theories and tools are ongoing. Azfar Basunia is a sophomore majoring in Biological Sciences with a concentration in Cell and Molecular Biology at the University of Chicago.

References 1. Venter, JC et al. (2001). “The sequence of the human genome” Science 291 (5507): 1304–1351. 2. Orgel, L.E. , Francis, Crick. “Selfish DNA: the ultimate parasite.” Nature. 17 April 1980. Web. http://www.nature.com/nature/journal/v284/n5757/pdf/284604a0.pdf 3. Makalowski W, Mitchell GA, Labuda D. Alu sequences in the coding regions of mRNA: a source of protein variability. Trends Genet. 1994;10:188–193 4. Crick, Francis. “Ideas on Protein Synthesis.” NIH. Oct 1956. Web. <http://profiles. nlm.nih.gov/SC/B/B/F/T/_/scbbft.pdf>. 5. “The Nobel Prize in Chemistry 1989.” Nobelprize.org. Web. <http://www. nobelprize.org/nobel_prizes/chemistry/laureates/1989/index.html>. 6. “Thomas R. Cech: Exploring the New RNA World.” Nobelprize.org. Web. <http:// www.nobelprize.org/nobel_prizes/chemistry/laureates/1989/cech-article.html>. 7. Visel, Axel; Bristow, James; Pennacchio, Len A. (2007). “Enhancer identification through comparative genomics”. Seminars in Cell & Developmental Biology 18: 140–152 8. “The 2009 Nobel Prize in Physiology or Medicine - Advanced Information”. Nobelprize.org. 6 Nov 2011 <http://www.nobelprize.org/nobel_prizes/medicine/ laureates/2009/advanced.html> 9. Gleichmann, U. S. “From Cardiovascular Prevention to Anti-aging Medicine: Influence on Telomere and Cell Aging.” Dtsch Med Wochenschr 136.38 (2011): 1913916. 13 Sept. 2011. Web. 18 Nov. 2011. <http://www.ncbi.nlm.nih.gov/

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pubmed/21915807>. 10. “The Nobel Prize in Physiology or Medicine 2006.” Nobelprize.org. Web. 06 Nov. 2011. <http://www.nobelprize.org/nobel_prizes/medicine/laureates/2006/>. 11. Lu R, Maduro M, Li F, Li H, Broitman-Maduro G, Li W, Ding S (2005). “Animal virus replicaton and RNAi mediated antiviral silencing in C. elegans”. Nature 436(7053) 12. Jiang M, Milner J (2002). “Selective silencing of viral gene expression in HPVpositive human cervical carcinoma cells treated with siRNA, a primer of RNA interference”. Oncogene 21 (39):6041–8 13. Grimm D, Streetz K, Jopling C, Storm T, Pandey K, Davis C, Marion P, Salazar F, Kay M (2006). “Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways”. Nature 441 (7092): 537–41 14. “Institute for Human Gene Therapy Responds to FDA -- Almanac Between Issues 2/14/2000.” Penn: University of Pennsylvania. 14 Feb. 2000. <http://www.upenn.edu/ almanac/between/FDAresponse.html>. 15. Strengthening Forensic Science in the United States: A Path Forward.” The National Academies Press. 2009. Web. <http://www.nap.edu/catalog.php?record_ id=12589>. 16. “Genome.gov | Press Photo: DNA Double Helix.” Genome.gov | National Human Genome Research Institute (NHGRI) - Homepage. Web. <http://www. genome.gov/pressDisplay.cfm?photoID=96>.

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UCHICAGO

“If our brains were so simple…” Minding the Gap William Dague

ne of Sir Isaac Newton’s most important insights was ness come from? This is a daunting question, but scientific not that there was some attractive force between Earth models may be able to help. Few would argue that water is and the apple, but that the very same attractive force anything more than two hydrogen atoms bonded to an atom kept the planets in motion around the Sun. He gave science a of oxygen. It is purely a physical system, and by virtue of great gift: the assumption that the physical laws are universal. this system’s particular arrangement it has certain properties. With that, Newton grounded the very heavens, formalizing No one thinks, “I experience water as wet, therefore I can what man had previously attributed to the gods. The notion find wetness somewhere in the basic structure of water;” the that nothing exists outside of the physical world seems central absurdity in the statement is obvious. Wetness is a property to the general philosophy of modern science. The universe is of water that exists on a completely different scale from its a physical entity which can be described entirely in terms of hydrogen bonds, yet it rests entirely within those fundamenphysical relations. Indeed, it seems that this perspective has tal relations. We may call such a property emergent; it is a already allowed science to reach heights of understanding characteristic of a system that exists on a higher level than that once appeared to be completely outside the bounds of its underlying causes [2]. If the human mind is the result of human reasoning. But what about what lies underneath hu- purely physical interactions, then perhaps we can view the man reasoning? Applying the so-called physicalist principle, mind as an emergent property of a particular arrangement of existence is physical, to our conception of the mind may be physical phenomena. Consciousness then, in this view, is the vital to furthering our understanding of the world and our physical world playing out in accordance with physical laws. place in it. Emergence is a recurring pattern in nature. Take, for Recent advances in neuroscience, psychology, biology, example, the behavior of termites. Individually, the actions of physics, and computer science seem to be converging toward a termite may seem to be chaotic and disorganized, but the aga model of the mind that exhibits a strong correlation with the gregate of all the actions of all the termites in a colony converges states of a physical system, the brain. This is an interpretation to form a larger overall structure, namely a termite mound. that we are all comfortable with on one level. With 43% of These mounds are complex, but clearly structured from our North Americans regularly takperspective. A biologist might ing mood altering prescription point out that this structure is drugs and with America’s multievolutionarily beneficial; it helps billion dollar alcohol industry, control the temperature of the When viewed at this scale there is a certain confidence colony, etc. A chemist would the termite mound is implicit that a change in our physiolpoint out that the enzymes in the ogy will alter our perceptions termites require a very narrow in the quantum process and [1]. However, when confronted temperature range to function entirely dependent on it, but with the issue of his own conproperly as catalysts for reacsciousness the average person tions. A physicist may explain it is not obvious from such a is tempted to think, “Surely, I that the molecules themselves fundamental level am more than just a skull full are the result of many atomic of chemical reactions.” There is processes requiring specific enan apparent disconnect between ergies. They would all be right, our intuitive understanding of each one appealing to a more experience and our rational understanding of the world. A fundamental relationship to reduce the overall system to a few examples from philosophy, mathematics, and biology will simpler and more general set of principles. When viewed at help us navigate through the fog of this cognitive dissonance. this scale the termite mound is implicit in the quantum process They will serve to construct both theoretical and empirical and entirely dependent on it, but it is not obvious from such bases for a physical model of conscious. a fundamental level. Are we justified in reducing complex phenomena like the evolution of mound building termites to Theoretical Feasibility interactions simple enough to be written down? The work of Human consciousness is a complex beast. How can we think one well-know computer scientist suggests that we may be. of the mind in strictly physical terms? Is it possible, even in In 1986, Chris Langton wrote a simple computer protheory, to ascribe all the nuances of our experience to the gram that exhibited some unexpected properties. It went sequential firing of networked neurons? Where does conscious- something like this: imagine a large two-dimensional grid

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UCHICAGO of white squares. In the middle of this grid lives an ant that obeys two simple rules: • At a white square, turn 90° right, flip the color of the square to black, and move forward one unit. • At a black square, turn 90° left, flip the color of the square to white, and move forward one unit. As the ant moves about by these rules the grid begins to take on a complex, even chaotic appearance. The ant continues to wander around, changing the board into a chaotic mass of black and white pixels. Suddenly, after about 11,000 steps the ant begins a 104-step loop, builds a “highway” (mound) and goes off to infinity. How did this structure emerge from such a tangled mess? This is a determined system: every step is completely prescribed by two simple rules, so where is this behavior hidden? This is a question that has stood as a challenge to many mathematicians. Langton’s ant is a member of a class of computer simulations, called- not accidentally“turmites.” There are many similar, more complex simulations being studied in an effort to understand this birth of order out of chaos. No one questions, however, that such a connection exists, encoded in these basic instructions. As this example

illustrates, a few basic relations can give rise to unexpected and complex phenomena. Experimental Evidence If we posit the mind as grounded in relations determined by physical law, then we would expect to see a close connection between the mind and its physical context (ex. the brain, body, surroundings, etc. ). The work of Prof. Nancy Burley of University of Illinois at Urbana-Champaign is one of many examples of recent scientific observations that challenge our intuitive picture of this connection. Her 1986 study suggests that changing the color of the identification tag on a male zebra finch can alter the primary sex ratio of its offspring [3]. In her experiment she and her team observed the mating behaviors of males with different colored leg bands. She found, not surprisingly, that females preferred to mate with males that had brightly colored bands (red or orange) over those with darker colors (green or black). In the absence of a supposedly more attractive male, females would mate with a less desirable partner. What was surprising, however, was that in cases where females were able to mate with brightly tagged males

Figure 2: 10,000 iterations. Reproduced from [6]

Figure 1: after 1,000 iterations of the rules. Reproduced from [6]

With this materialist perspective, that which was once thought to be inaccessible, our consciousness, seemingly becomes graspable

Figure 3: After 13,000 iterations we clearly see the highway emerge! Reproduced from [6]

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UCHICAGO the resulting offspring had significantly larger percentage chology demonstrates remarkable control over its underlying of male offspring compared with those of the less attractive physiology, but there are many more instances where it does male parent. This shocking result that was not immediately not. The discovery of the placebo effect has not mitigated the accepted in the ornithological community: why should the use of medications in treatment of disease. It has, however, color of the tag on a bird have any correlation to the gender of shown us that our minds and bodies can no longer be seen its offspring? Her procedure has been repeated at least twice as two distinct entities. The examples presented above serve since [4]. The connection stands. This challenges our intuition not to establish any particular model, but to help us grasp the about how the external environment can influence biological notion of a physical mind in the context of a physical universe organisms. What is the connection between the psychological and to begin a dialog in the spirit of Newton. state of a finch during intercourse and its physiological state? The belief that we can completely model the complexiWhat of the obedience to the underlying principle of natural ties of the human mind as an aggregate of simpler physical selection for sexual attractiveness? Is evolution of the zebra processes, the physicalist approach, is a perspective that is not finch species somehow accelerated through its psyche? only reasonable based on the evidence discussed so far, but If we assume that the bird’s nervous system is analogous, may allow us to comprehend our own experiences in a unique to our own (albeit far simpler), then we should consider the and profound way. Indeed, the implications of this perspecpossibility that there are complex but analogous relations in tive could be far reaching. The studies of artificial intelligence, the human case. This would suggest an intimacy between the psychology, neurology, sociology, economics, and language mind and the body that is not obvious from our own experi- would all benefit greatly from a comprehensive model of the ences. As another example of this human mind. The physicalist outclose connection, let us look at look may provide avenues for exone case of what is called neural ploring areas not conventionally top down control of physiology. considered under the realm of the There is a certain confidence A 2002 study by Goebel et. al. at physical world (ex. anthropology) that a change in our physiology the University of Essen, Germany, using new, more comprehensive showed that human beings could techniques. This unification of will alter our perceptions be taught to suppress their own subjects might prove to be a immune system through a kind powerful resource in our quest of Pavlovian conditioning [5]. to understand our universe. But Patients were given an immunosuppressant that was mixed first we need to believe that it’s possible. Emergence may with a distinctly flavored drink every twelve hours for three allow us to bridge the gap between the brain and the minds days. A week later, the patients were given the same drink, we all experience. While it may not yield the answers to all this time with a placebo in place of the immunosuppressant. of our questions about the mind, treating our human experiWhat the researchers found was that by a bizarre placebo ence as physical and knowable helps make that gulf between effect, the taste of the drink was itself enough to mimic the the self and science seem surmountable. With this materialist effects of the drugs. The subjective experience of tasting had perspective, that which was once thought to be inaccessible, a direct influence on the body’s workings at the cellular level! our consciousness, seemingly becomes graspable. We should This stands amid many, interesting placebo effect studies that not allow our fear of determinism keep us from reaching for emphasize the mysterious connection between the mind and a more complete picture of human experience. Though we body and suggest that the two are more closely related than do not know all the processes occurring between our biology had been anticipated. and our psychology, understanding that they can both be It may seem at first that the zebra finches and the placebo conceived as physical systems bound by physical law is the effect put emergence on shaky ground, but further consideration first step on a thousand mile journey toward understanding brings us back to the termite mound. The mound appears to ourselves. direct the actions of individual termites: they congregate in certain chambers and move via prescribed pathways. But the William Dague is a third-year physics major in the college at the mound is still completely determined by the actions of those University of Chicago. He is interested in cosmology and theoretical termites. While it is beneficial, ensuring the safety and survival astrophysics as well as in computer simulations of the large-scale of the colony, the mound’s existence relies entirely on termites universe, especially those that incorporate the principles of chaos. being the sort of creature who builds mounds. This “limited top-down control’ relationship is made clear in the case of the placebo effect. There are many instances where human psyReferences 1. Burley N. Sex-Ratio Manipulation in Color-Banded Populations of Zebra Finches. Evolution. 1986 Nov. Vol. 40 No. 6 Available from: http://www.jstor.org/ pss/2408947 2. Von Englehardt N, Witte K, et. al. Sex Ratio Manipulation in Colour-banded Populations of Zebra Finches [chapter from an online manuscript]. Cited 2012 January 28. Available from: http://dissertations.ub.rug.nl/FILES/faculties/ science/2004/n.b.von.engelhardt/c2.pdf 3. Searle, John. Minds, Brains, and Science. Cambridge, Massachusetts: Harvard

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University Press; 1984. P. 22 4. Anxietycentre.com [homepage on the Internet]. Anxiety Statistics. c. 1987-2012 [cited 2012 January 28]. Available from: http://www.anxietycentre.com/anxietystatistics-information.shtml 5. Goebel MU, Trebst AE, Steiner J, Xie YF, Exton MS, Frede S, Canbay AE, et. al. Behavioral conditioning of immunosuppression is possible in humans. FASEB J. 2002 Dec;16(14):1869-73. Available from: http://www.ncbi.nlm.nih.gov/ pubmed/12468450 6. http://flashi.wordpress.com/2008/02/06/langtons-ant/

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CMU UCHICAGO

The Alien Ceres: Promises and Precautions of Modern Agriculture Niloufar Hafizi

he image is familiar and nearly universal: a deity bear- environmental degradation associated with the intensive farming grains of wheat or pictured next to a plow, called ing and chemical usage of the initial Green Revolution. To the Ceres, Osiris, Lord Balaram-the name does not matter. benefit of many, agricultural output has increased as a result A stable food supply is a cornerstone and major concern of of the biotech revolution, but there is evidence that it has had any civilisation; for this reason agricultural deities are a staple the reverse effect on those in need of economic progress [6]. of nearly every pagan pantheon. Today’s Ceres, however, A basic understanding of the process involved in creating has undergone a radical change. Her graceful robe has been genetically modified organisms [GMOs] is extremely helptransformed into a stylish, crisp suit, with business cards in ful when reading about industrial agriculture. A genetically the pocket bearing the logo and name of a biotechnology modified organism has had one or more foreign genes selected company. She still holds grain, but it is clasped more closely from another organism inserted into its genome [7]. Genes to her designer-clad chest, and held aloft so that only those are typically not inserted singularly but as a package includwho are already strong and vigorous may reach it. Those in ing promoter and terminator regions and a marker, together developing countries, where agriculture is not only an under- known as a cassette. An unaccompanied gene would not be valued sector of the economy but the basis of their tenuous able to function without these mechanisms, which indicate livelihood , are left with empty hands. when and where the gene is activated and when its transcripWorld hunger is not a new issue, and recent agricultural tion ceases [4, 7]. Most cassettes are inserted at random into innovation is by no means the sole reason for continuing hunger the host organism, which may disrupt the functions of other or rural poverty in developing countries [1]. However, biotech- genes, and it is often necessary to use marker genes to ascertain nology certainly does complicate the approach. Despite the that the desired gene has become part of the host’s genome . latter’s advertisement of itself as a solution, it has presented new Once confirmed, genetically modified status is also verified [4]. legal and ethical challenges without overwhelmingly successful The distinction between ‘genetic modification’ and ‘transactivity on the solutions front of this enduring issue[2]. Over genic’ is largely overlooked but is of great importance for two centuries ago, Thomas Malthus famously predicted mass understanding the disputes over the products of biotechnology. starvation as the geometrically expanding human population Biotechnology’s GMOs, or ‘Frankenfoods’ [8] as they are somewould eclipse the arithmetically sluggish growth of the food times called in the media, refer specifically to foods modified supply. One of the several factors which his 1798 Essay on so as to be transgenic. Mankind has been genetically modifying the Principle of Population had not taken into account was food since the beginnings of agriculture over ten thousand that agriculture was undergoing a years ago. Nearly everything we transformation that would result consume has been genetically in exponential growth to match modified, sometimes to the point that of the human population [3]. where it is unrecognizable from Nearly everything we Beginning in the mid-twentieth its ancestor . Unlike artificial consume has been century, the Green Revolution selection, genetically engineering not only prevented devastating an organism creates transgenic genetically modified, starvation in Latin America and products which contain genes sesometimes to the point parts of Asia through the heavy lected and transferred from other use of fertilizer, herbicides and species. A transgenic organism where it is unrecognizable hybrid varieties, but also raised has been genetically modified, from its ancestor production of some grain types in but not all genetically modified Mexico by 50 percent and turned organisms are transgenic. Biotech India into an exporter rather than companies such as Genentech an importer of food grains [4]. Unfortunately, there arrived prefer to flout the term ‘engineering’ because it connotes a a time in the 1990s when it became clear that starvation and high degree of precision. Agricultural biotech companies like malnutrition had not been eradicated. Extending the same to claim that farmers using conventional breeding techniques techniques was no longer possible, because the land wore out or radiation employ a more hit-or-miss kind of process, since and productivity tended to decrease after an initial boom . the interactions of the genes in the entire organism may or A new method was needed. The biotechnological revolution may not generate the desired results [4]. The implication, of publicized itself as the succeeding savior, capable of feeding course, is that the insertion, or engineering, of specific genes is the 800 million hungry left in the world and preventing the a superior method. The term engineering may be misleading in 12 THE TRIPLE HELIX Spring 2012 Book 1.indb 12

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UCHICAGO this case, since the process of inserting genes from one species into another, or even tinkering with genes in a single species, can be as imprecise as conventional approaches. Not only is its success uncertain, but it may also have unforeseen effects due to unknown linkages or unpredictable gene insertion [7, 9]. The following cases about GMOs serve to illuminate the downsides of what biotechnology has meant for parts of the developing world. The social and economic effects of biotechnology in less developed parts of the world can be ignored in the media haze of slogans involving puns based on Gothic novel titles and exaggerations of science . All of these effects are ironic, considering that one major bastion of initial biotechnology promotion was the potential alleviation of hunger.

Despite [biotechnology’s] advertisement of itself as a solution, it has presented new legal and ethical challenges without overwhelmingly successful activity on the solutions front of this enduring issue

Biotechnology from the beginning was dominated by a sense of business [6, 9]. The very first genetically modified plant, a tomato that did not rot as quickly as the conventional tomato, was the child of the California company Calgene [4]. Nowadays, a handful of corporate life science conglomerates, which formed to combine patent claims, controls most of the market. The profit-driven environment thus creates shifts within the attitudes and purposes of science. An open environment where information is shared freely, a feature of the struggle to understand what genes are and the genetic makeup and growth process of corn sixty years ago [5], no longer exists. Scientists with humanitarian aims must seek grants from governments and charitable foundations, of course. They probably will also need to struggle through thickets of intellectual property rights and patent claims, some of which historically have been claimed by more than one company [4], before making their findings available. An excellent sample case is the invention of vitamin-A enhanced rice, or “golden” rice . The golden–yellow hue for which the engineered rice is named comes from the presence of beta-carotene, also found in carrots. This pigment is a precursor of vitamin A and was researched for eight years in order to address the problem of vitamin A deficiency in the developing world, estimated to account for about a quarter of all global malnutrition-related diseases [4, 10]. People lacking vitamin A often become blind

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and immunologically compromised. The goal of Professors Ingo Potrykus and Peter Beyer, the creators of golden rice, was to find a solution to this problem. However, in the course of their research, they had infringed seventy patents belonging to thirty-two different corporations [4]. To complicate matters further, they ran out of funding during their labours. Beyer was compelled to accept funds from the European Union, the corporate partners of which had rights to the results. The researchers found themselves forming a deal with AstraZeneca which gave the company license to the technology but allowed small farmers with annual incomes under $10,000 to use the technology for free once it was prepared for distribution. The outcome was not as dismal as it could have been, but Potrykus could not help but express his annoyance with the necessity of the proceedings in a paper: “It seemed to me unacceptable…that an achievement based on research in a public institution and exclusively with public funding and designed for a humanitarian purpose was in the hands of those who had patented enabling technology earlier or who had sneaked in a material transfer agreement...” [11]. Business competition was here less a motivation for innovation than an opportunity for domination.

Reproduced from [17]

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CMU UCHICAGO Patents and property rights are not obstacles for only well-intentioned researchers. They impact developing countries directly in the phenomenon known as biopiracy, or bioprospecting. Given the paucity of genetic variety in the developed world, its corporations send out ‘gene hunters’ to the cradles

sought to protect the genetic treasure troves of communities, giving states sovereign rights over such biological resources and indigenous groups rights to their traditional strains and inherited knowledge. Commercial users of the knowledge would be required to distribute profits with equity [4, 13]. The fact that such a treaty is needed is a jarring indicator of what modern agriculture has become . The golden rice and basmati rice case studies present some of the major problems To the benefit of many, modern agribusiness presents to struggling farmers: the abuse of GMOs created for humanitarian purposes, the difficulty of agricultural output has pursuing such research, and the abuse of the cultural rights increased as a result of the of ethnic communities by companies from countries where monoculture is eliminating genetic variability. biotech revolution, but there A third example from Africa will round out the grouping: is evidence that it has had during the African famine of 2002, the United States offered food aid packages of corn to the afflicted countries. Since grain the reverse effect on those in varieties are not milled separately in the United States, any need of economic progress corn sample most likely contains genetically modified corn. Three countries -Zimbabwe, Mozambique, and Zambia- all refused the aid in the midst of starvation. Zimbabwe eventually grudgingly accepted on the condition that the corn be of agriculture and variety for new strains [12]. The activity is milled and free of seeds which could be planted. Zambia and not unprecedented – Columbus and his sailors, returning to Mozambique still flatly refused. In addition to health and Spain in gory triumph, brought New World crops as part of safety concerns, the reasons cited were economic and environtheir array of loot [5]. Bioprospecting can be done in an ethical mental precautions. Impoverished farmers in countries such way, with the consent of the source country and a sharing of as Zambia are able to sell their products to many countries the benefits, or in a manner akin to plunder. The following in the European Union under the label of ‘GM-free’. If ‘GM’ example illustrates the latter: in the 1990s RiceTec, a Texas seed from American donations were to contaminate Zambia’s company that uses molecular tools in its product designs, fields, the farmers may be left with no market [4]. Due to their patented what it claimed were new strains of basmati rice. legitimate concerns, these three countries to this day refuse These new ‘inventions’ were bred by crossing dwarf rice with to import grain and corn aid from the United States unless it basmati from Pakistan [4]. is first ground into powder. This effective solution prevents The consequent uproar was not surprising. Basmati has the food from being planted [6, 9]. been cultivated in Pakistan and northern India for millennia. The threat to existing, low-technology agriculture in areas It struck many as ludicrous that a traditional variety could be that are too poor to be targeted as consumers of biotechnology tweaked and claimed by a foris another part of the repertoire eign company. The possibility of concerns for the developing of harm to exports from the auworld [6]. New genetic engineerIncreasing global thentic growing regions and the ing techniques are costly, favourattention, particularly alleged misuse of the name ‘basing corporations who have the mati’ by RiceTec led to a lawsuit means to develop them, and are from governments and [4, 13]. The Indian government unlikely, due to legal issues, to international organizations, petitioned and fifteen of twenty be available for humanitarian of the patent claims were overdistribution as Green Revoluis thus carving the way turned by the United States Patent tion products were. Whatever to some changes in how Office in 2001 [4]. However, the biotechnological findings that larger issue highlighted by this may be advantageous for subbiotechnology operates and case was the subject of patents sistence farmers will most likely affects an already beleaguered and cultural rights. The idea of lead them into debt, especially taking out a patent for a tradisince biotechnological products agricultural scene in lowertional plant had not before been require continued investment. income countries necessary, but the patent world The greater efficiency of farms had changed. At a meeting of the with access to biotechnology United Nations Conference on means that the disadvantaged Environment and Development farmers can easily be outcomat Rio de Janeiro in 1992, one of the topics was the United Na- peted if they raise similar crops for export. The presence of tions Convention on Biological Diversity. The resulting treaty genetically modified organisms from aid or on a neighboring

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UCHICAGO farm in any country may even threaten the current livelihood of farmers who export under a transgenic-free label. Intervention by NGOs can better the situation, but the behemoth farms on their own have little reason to work with small farmers or change their methods. On an optimistic note, agribusiness is taking a new approach which contains itself to the single plant species’ genome, reducing the risk of foreign genes infiltrating native gene pools [14]. Biotechnology companies usually control all stages of production, beginning with research. This has led to the development of plant seeds which engender sterile offspring, forcing farmers to purchase crop seeds annually. Viable seeds cannot be used either, because patent laws allow companies to own living plants and the seeds which the company has ‘created’. Farmers are usually forced to sign contracts agreeing to dispose of new viable seeds. Any farmer who continues the traditional practice of saving and using seed from last year’s crop is at risk of being sued [6]. Equally insultingly, corporations and individuals infringe upon cultural tradition by patenting long-existing varieties of regionspecific crops produced with new methods. An overhaul of patent laws and more effective international resolutions are is clearly in order to prevent corporate domination. While the humanitarian side has partially won the legal debate, as in the RiceTec and the golden rice cases , it is not always victorious. Fortunately, agriculture and biodiversity are frequent topics on the international agenda and a subject of investigation for United Nations committees and agencies [15]. Research groups such as the Consulting Group

for International Agricultural Research make an effort to create gene banks to preserve variety, and some governments such as in India have begun to codify and store indigenous knowledge in order to protect it. Positive efforts are accompanied with negative reactions. The consequences above have contributed to the general antibiotechnological sentiment that, while subsiding, continues to prevail in Europe [9] .The products of biotechnology were banned from Europe for a long duration, and now member states are able to individually opt for bans if products are unsafe [15]. In parts of the developing world, recent years have seen a rise in demand for local and organic agriculture. These have their own limitations, but could be important as the use of GMOs increases globally [9, 16]. Increasing global attention, particularly from governments and international organizations, is thus carving the way to some changes in how biotechnology operates and affects an already beleaguered agricultural scene in lower-income countries. GM crops are most likely here to stay, and with the gradual onset of regulation and reconsideration of biotechnology’s goals and impacts, a new vision of Ceres is presented. More benign, as was first promised, her posture is less imposing and her expression is less ruthless. She has not changed her garments-it is probably Reproduced from [18] too late for that-but this time she appears to hold out the fruits of her power, bestowing rather than grasping. Niloufar Hafizi is studying Economics at the University of Chicago.

References 1. Meijerink G; Roza P. The role of agriculture in development. Markets, Chains and Sustainable Development Strategy and Policy Paper, no. 5. 2007. Stichting DLO: Wageningen. Available from http://www.boci.wur.nl/UK/Publications/. 2. Watson JD; Berry A. DNA: The Secret of Life. Alfred A. Knopf, New York, 2003. 3. Bucholz TG. New Ideas from Dead Economists, Second Revised Edition. Plume, Penguin Group, New York, 2007. 4. Pringle P. Food, Inc. Simon and Schuster, New York. 2003. 5. Endersby J. A Guinea Pig’s History of Biology. William Heinemann, London, 2007. 6. Miller M, Cutler J. Genetically Modified Crops in Africa. United Nations Environment Programme. Encyclopedia of Earth. April 2007. Available from http:// www.eoearth.org/article/Genetically_modified_crops_in_Africa. 7. University of Nebraska Lincoln. Overview of the Process of Plant Engineering. 2001. Available from http://agbiosafety.unl.edu/education/summary.htm. 8. O’Neill M. Geneticists’ Latest fear of Discovery: Public Fear of ‘Frankenfoods’. The New York Times. 28 June 1992. Available from http://www.nytimes.com/1992/06/28/ us/geneticists-latest-discovery-public-fear-of-frankenfood.html?scp=6&sq=Frankenf oods&st=cse. 9. Blatt H. America’s Food. Massachusetts Institute of Technology Press, Cambridge, 2008. 10. World Bank. 2007. World Development Report 2008. Washington: The World

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Bank. 11. Potrykus I. Golden Rice and Beyond. Plant Physiology. March 2001; 125(3): 1157-1161. 12. Biopiracy and appropriation of traditional knowledge. Third World Network. 2010. Available from http://www.twnside.org.sg/access_7.htm. 13. Sahai S. The basmati rice patent. Gene Campaign. 22 July 2000. Available from http://www.genecampaign.org/Publication/Article/IPR/basmati%20PatentnotMisunderstanding.pdf. 14. European Commission Joint Research Centre. Next-generation biotechnological plant-breeding techniques. GMO Safety. 18 May 2011. Available from http://www. gmo-safety.eu/news/1322.biotechnological-plant-breeding-techniques-jrc.html. 15. Food Safety-From Farm to Fork. European Commission. Dec 2011. Available from http://ec.europa.eu/food/food/biotechnology/gmo_ban_cultivation_en.htm 16. Aldred J. Worldwide Increase in GM Crops, Reports Show. The Guardian. 13 Feb 2008. Available from http://www.guardian.co.uk/environment/2008/feb/13/gmcrops. food. 17. Teosinte, Ancestor of Corn [Image on the Internet] 2002 [cited 2012 Feb 24]. Available from: http://www.fao.org/docrep/005/y3841e/y3841e08.jpg 18. http://www.ars.usda.gov/images/docs/12255_12449/DSCN0570.JPG

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UCHICAGO

Of Resources and Trust: The Battle for STD Screening in Low-income North America Sami Ismail

hen watching 32-foot long trucks speed down a freeway, one may assume they contain fuel, food, or merchandise, but most would never guess that these trucks may carry equipment for sexually transmitted disease (STD) screening and prevention [1]. Such large mobile vehicles may appear better suited to the food venders that line tourist hubs than to health clinics, but they are part of a creative initiative by public health advocates like the Center for Disease Control (CDC) to find effective and replicable solutions that can halt the proliferation of STDs among poor

North American youth. Teenagers in poverty now face a spread of STD infection at rates higher than ever before seen, while proper sexual education and the medical services needed to stop STD transmission have generally been absent from the communities that need it most [2]. Because traditional clinics are viewed as alien and even hostile entities, they have often failed to provide medical assistance and screening to at-risk patients [3]. To add to problems of outreach and community trust, traditional clinics are expensive and have been inefficient in securing resources. Why do so few teenagers in low-income Reproduced from [24]

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UCHICAGO areas throughout North America get the medical treatments and of young women are likely infected with HPV [8]. Though most sexual education they need and what can be done about it? A of the 100 different strains of HPV are not notably harmful close look at the manner in which STDs have spread and why and may cause only slight abnormalities within the cervix, traditional screening methods have failed holds the answer. approximately 15 strains of HPV are considered high-risk Life-threatening or sterilizing illnesses may not be the first types, especially HPV 16 and HPV 18, and are responsible for thing that come to teens’ minds when they talk about or have cancer-causing effects including cervical cancer, anal cancer, sex, but as recent studies and statistics have shown, practicing and vulvar cancer. [9]. unsafe sex can ruin teens’ reproductive health and even cost Commonly known epidemiologic risk factors for cervical them their lives. While in the eighties and nineties, the spread cancer include low socio-economic class, early age of onset of of AIDS via prostitute contact by male clients and promiscuous sexual activity, multiple sexual partners (or male partners with homosexual relations was the main public health concern, multiple other partners), and smoking. Another debilitating recent concerns have shifted to combat the explosion of STDs and often stigmatizing disease caused by HPV is condyloma, within predominately heterosexual teenagers in low-income which cause visible warts on the genitals of those infected, urban areas in North America, including Los Angeles, New resulting in lowered health and heighted sexual sigma for the York City, Toronto, Vancouver, New Orleans and Boston [4]. patient. HPV infection depends on many factors including Currently, one in every four women between the ages of 14 the strength of the individual’s immune system to fight infecand 19 in the United States has a sexually transmitted disease, tion, smoking as an additional co-factor and many unknown and of youth who have admitted to being sexually active, local factors in the sites of infection. Sexually active young infection rates soar to an unprecedented 40 percent at any teens and young adult women are very likely to have HPV one time, of which Human Papillomavirus (HPV) and Chla- infection but are able to clear this infection over time if the mydia constitute 18 and 4 per infection is not persistent. Percent of infections, respectively sistent infection, however, can [2]. In Canada, STD rates are inlead to precancerous changes on creasing rapidly among youth the cervix. Oncogenic strains of For screening to become under 25 years old, with the rate HPV can dominate the cervix widespread in at-risk of Chlamydia reaching 1,139 out before symptoms arise causing of every 100,000 women [5]. HPV a state known as “precancer,” communities, there must and Chlamydia are both serious wherein lesions form within the be trust between public infections without found cures, epithelium of cervix cells [10; 9]. but consistent condom use and The fact that HPV is asymptomhealth professionals and the regular sexual health check-ups atic heightens the likelihood of communities they are trying can exponentially decrease the disease spread as asymptomatic health risks presented by both patients rarely seek medical atto engage infections. These reasonable meatention until physical discomfort sures have not been followed, and illness becomes apparent. however, because there has not Unfortunately, by that time mabeen sufficient sexual education to educate the poorest North lignant cancer has manifested within the cervix, treatment American youth about the basics of safe sexual relations. [6]. may require surgery or in advanced cases, chemotherapy and STD prevention measures need to take into account both the radiation, which can potentially affect [9]. The fact that HPV scientific and social aspects of STD prevention crucial to help- is asymptomatic heightens the likelihood of disease spread as ing North America’s most at-risk teenagers. asymptomatic patients rarely seek medical attention until physiTeens living in poverty suffer from a higher frequency cal discomfort and illness becomes apparent. Unfortunately, of food insecurity and limited access to quality medical care if a cancer is within the cervix, treatment may require surgery compared to the wealthier members of their peer group. [7]. As or in advanced cases chemotherapy and radiation, which can a result, teens in poverty-stricken areas are half as likely to be potentially affect future fertility or pregnancy outcomes. healthy in general compared to teenagers in higher economic Chlamydia is an asymptomatic STD that many individuals brackets, and this gap is particularly noticeable when sexual spread without even realizing they are infected. Chlamydia health is investigated. Youth opposition to regular asymp- is the second most common sexually transmitted disease in tomatic screening has resulted in a huge outbreak of HPV youth, and is a ‘silent killer’ that contributes to sterility and and Chlamydia, two of the most virulent STDs, throughout heightens the risk of cancer within individuals infected by economically impoverished areas across North America. HPV HPV [2, 10]. Chlamydia’s bacterial cells can bind to vacuoles is considered one of the most common STDs in the world, and within uterine cells, thus avoiding detection and termination public health efforts to combat it have been largely unfruit- by human lymphocytes (white blood cells) [11]. Because of this ful due to ignorance within the general populace regarding molecular evasion, Chlamydia can remain present within the HPV’s devastating effects on sexual and reproductive health. human body for years without being located and killed by the Approximately, 80% of all sexually active people may have a host’s immune system. During this latency period, the host’s HPV infection during their lifetime. At any point in time, 30% body quickly circulates white blood cells through the uterus,

Book 1.indb 17

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UCHICAGO attempting to fight the infection, and this increased blood flow in public health surveys had any knowledge that HPV was causes inflammation within the fallopian tubes [12]. Due to a common STD that results in cervical cancer [19]. Similar the violent nature of this blood circulation, many areas of the ignorance to the effects of HPV was seen in Canada, wherein uterus become severely damaged, leading to incorrect uterine only thirty-nine out of one hundred of young women in Tofunction and eventual sterility. The tragic reality is that Chla- ronto knew that they should regularly obtain pap smears, mydia and HPV tests to avoid these negative consequences are while less than one teen in ten in that area had any idea what painless and involve simple techniques requiring just small HPV was at all! amounts of urine or sputum to make an accurate diagnosis Low screening rates also revolve around the issue of trust. [12], but they can only take place if patients are comfortable For screening to become widespread in at-risk communities, with their local testing resources and are adequately educated there must be trust between public health professionals and to the risks unsafe sex poses to their health. the communities they are trying to engage. Among many Recent scientific breakthroughs have provided treatments individuals living in poverty in North America, especially to combat STDs. Chlamydia, if detected early, can be cured those whose parents are of color and have struggled to combat with a thorough course of antibiotics [13]. While Pap Smears, racist bigotry, the mistrust of many governmental activities which are used to investigate whether cells taken from a pain the past continues to influence a feeling that governmenttient have been affected by HPV infection, are appropriate for backed agencies often attempt to increase the burdens on the the young adults in low income poor ethnic minorities [20]. As communities, teenagers are ensuch, both poor teens and their couraged instead to use the HPV parents find it hard to trust The real kick to all STDs vaccine and educate themselves their health care providers and in low-income areas will as to the risks of irresponsible government-backed public health sexual activity as their main advocates, which they feel may come from continued effort resources to fight HPV [14, 15]. not be working in the youths’ best on the part of public health In Canada, the federal agency interests as they are connected on health, Health Canada, has to state organizations perceived programs to work with been working in conjunction with as being racially biased. Rumors local communities to spread provincial health ministries to are often circulated within poor reach women at risk for cervical urban communities that STD awareness of the risks cancer of any income level [16]. screenings don’t actually help involved in unprotected Such efforts are mirrored in the poor communities, and even United States by the Center for may increase STD rates. In the sexual activity and the need Disease Control and Prevention words of one African-American for increased approachability (CDC), which supports the pricommunity member “they [the vately funded National Breast and government] may not be telling Cervical Cancer Early Detection the full story [about HPV], which, Program, in which free Pelvic of course, we found out about tests and referrals to treatment for HPV and Chlamydia are syphilis and AIDS” [20]. Additionally, social factors like the given to women lacking health insurance [17]. Poor communi- perception that healthcare professionals are judgmental of ties, however, often feel that logistical issues make obtaining the youths’ sexual decisions and the fear of gossip by other free tests harder than they should be [3]. In both Canada teens that associate testing with promiscuity are major deand in the United States, clinics that give free sexual health terrents to many teens that would otherwise get screened services are often located in underserved inner cities, where [3]. Logistical concerns about collection methods, urethral outreach by these clinics to the communities that need it most specimen collection methods, long clinic waiting times and is rarely sufficient. Therefore, many at-risk teenagers either are fears of financially unaffordable clinical care (reflecting that not informed about their local health options, or deterred by free community clinics are not publicized sufficiently) within complaints from other low-income teens that have had a poor overburdened and poorly staffed clinics have discouraged clinic experience due to the bureaucracy. Thus, the number young adults from taking responsibility for their sexual health, of potential clinic goers and the amount of community trust adding to the discomfort and distrust many youths associate of local clinics declines [3]. with public health clinics [3]. While screening is among the most effective measures Traditional public health clinics have had only limited used to combat STDs, the practice of this preventative technique success in STD prevention due to the logistical expenses and in poverty-stricken areas has proven disappointingly low [18; social barriers of community distrust they have faced. The 3]. There are numerous methods to achieve that needed trust current economic recession has negatively impacted funding and convince poor North American youth of the benefits of for public health efforts in both Canada and the United States. screening, but none are quite as effective as education. The While the average per capita spending for all public health low amount of actual sexual education among low-income was the equivalent of $40.33 in 2007 (which was a decent, if teenagers has inhibited real progress in STD prevention. In not high number) before the recession was in full swing, it the American South, only three out of over thirty participants reduced to $40.25 per capita by 2009 [21]. A drop in 8 cents 18 THE TRIPLE HELIX Spring 2012 Book 1.indb 18

3/29/2012 7:56:55 PM

UCHICAGO may not seem significant, but when that figure is applied to the over 340 million inhabitants of the USA and Canada, it has major negative implications for funding. These cuts have resulted in a 30% decrease in clinic visits among all North Americans, with an even high number of poor youth being financially prevented from screening [22]. In addition to these staunch financial realities, young adults who reside in low-income areas have rarely been raised in households where discussions about safe sex were appropriate (assuming that both parents were present at all), and subjects such as inquiring about a partner’s STD history are often shunned [23]. Both subjects are seen as supportive of possible promiscuous behaviors and are thus rejected. In response to both of these challenges, creative and inviting methods from traditional public health advocates have been invented to meet the problem on a grass roots level. One method that challenged this communal shyness was the Mobile Clinic Initiative in Baton Rouge, Louisiana and the Mobile Medical Van in Hartford, Connecticut [1, 24]. Started in 2003, the MCI developed with the goal of being a transparent and open clinic initiative that invited all members of low-income Baton Rouge communities to use its services. MCI became viewed as a “good” idea by 97% of polled community members [1], while MMV in Hartford was able to attract at-risk individuals who would have simply refused screening at a hospital only a few blocks away. The outreach MMV projected was specifically directed to the poverty stricken youth of any sexual history and therefore led to a wider range of previously discouraged members of the Hartford community to get screened [24]. Why did these programs merit such acceptance? Because MCI and the MMV worked with outreach groups composed of actual community members that the patients could relate to and who made the patients feel comfortable. These clin-

ics’ ability to integrate socially with the atmosphere of the communities they were serving decreased community feelings of distrust and embarrassment. Because of these efforts, screening in both areas was higher than it had ever been for the poor demographics of both cities [3]. If similar outreach campaigns are taken in other cities throughout North America, the scourge of STDs could be reversed. Under current policy, aid, drugs, chemical tests, equipment and all other supplies for free clinics that were once provided in part through governmental aid now must be purchased with funding from individual private donors [25]. The number of free clinics specializing in STD prevention is decreasing, which is simply unacceptable when fully a quarter of American girls are infected with an STD, and the combination of Chlamydia and HPV can cause young ladies throughout North America to never reproduce or increase their risks of obtaining cancer. The real kick to all STDs in low-income areas will come from continued effort on the part of public health programs to work with local communities to spread awareness of the risks involved in unprotected sexual activity and the need for increased approachability between sexually active teenagers and personnel in public health. This effort should be paired with continued financial support for available health resources for all, as was seen with the Mobile Clinic Initiative in Baton Rouge and Mobile Medical Van in Hartford. Only with creative, open and trust-building programs like MCI and MMV can North American public health advocates reach out to low-income youths and cause lasting changes in STD prevention. Without such investments, the consequences to North America’s low-income youth may be devastating and tragically affect those communities for generations to come.

References

cervical-cancer-prevention. 14. US Department of Health and Human Services Office on Women’s Health [Internet]. Pap test fact sheet: 2009 [cited 2011 November 21]. Available from: http:// www.womenshealth.gov/publications/our-publications/fact-sheet/pap-test.cfm#q. 15. Public Health Agency of Canada [Internet]. Cervical Cancer Screening in Canada: 1998 Surveillance Report: 1998 [cited 2011 November 21]. Available from: http:// www.phac-aspc.gc.ca/publicat/ccsic-dccuac/index-eng.php. 16. Centers for Disease Control and Prevention [Internet]. National Breast and Cervical Cancer Early Detection Program: 2011 [cited 2011 December 5]. Available from: http://www.cdc.gov/cancer/nbccedp/screenings.htm. 17. Cohen DA et al. Repeated school-based screening for sexually transmitted diseases: a feasible strategy for reaching adolescents. Pediatrics. 1999 April; 104(6): 1281-1285. 18. Friedman, Allison and Hilda Shepeard. Exploring the Knowledge, Attitudes, Beliefs and Communication Preferences of the General Public Regarding HPV: Finding From CDC Focus Group Research and Implications for Practice. Health Educ Behav. 2007 June; 34 (3): 471-484. 19. American Social Health Association. [Internet]. Annual Report: 2010 [cited 2011 November 18, 2011]. Available from: http://www.ashastd.org/uploads/pdfs/ AnnualReportFY10.pdf. 20. Rietmeijer, Cornelis. The Role of STD Outreach Testing in Times of Dwindling STD Prevention Resources. Sexually Transmitted Diseases: Aug 2003; 30 (8): 659-660. 21. Van Devanter, Nancy. Prevention of Sexually Transmitted Diseases: The Need for Social and Behavioral Science Expertise in Public Health Departments. Am J Public Health. 1999 June; 89 (6): 815-818. 22. Liebman, Jon. Effectiveness of a Mobile Medical Van in Providing Screening Services for STDs and HIV. Public Health Nursing Magazine. Sept 2002;19 (5): p.345353. 23. Scott, Michael John. Republican tax cuts force free clinics to turn away needy [Internet]. [Place unknown]:Americare; 2011 [cited 2011 November 18]. Available from: http://madmikesamerica.com/2011/07/republican-tax-cuts-force-free-clinics-toturn-away-needy/. 24. http://www.oregon.gov/DAS/PEBB/images/websized/WorksiteScreening

1. Tanner, Lindsey. Study Finds 1 in 4 US Teens Has a STD. Huffington Post. 2008 March 12; 1-2. 2. Tilson, Elizabeth, et al. Barriers to asymptomatic screening and other STD services for adolescents and young adults: focus group discussions. 2004 June; 4:21. 3. Aral, Sevgi and King Holmes. Sexually Transmitted Diseases in the AIDS Era. Scientific American. 1991 Feb; 264(2): 64-66. 4. The Body : The Complete HIV/AIDS Resource [Internet]. Saskatoon, Canada: CDC News: 2002 [cited 2011 November 17]. Available from : http://www.thebody.com/ content/art18151.html. 5. Lee, Sin Hang et al. Molecular tests for human papillomavirus (HPV), Chlamydia trachomatis and Neisseria gonorrhoeae in liquid-bsed cytology specimen. 2009 April; 9:8. 6. Physorg: Science, Physics, Technology and Nanotechnology News: 2010 [cited 2011 November 24]. Availablehttp://www.physorg.com/news199986071.html. 7. Medical News Today [Internet]. Charleston, SC: Researcher Finds Link Between Chlamydia and Cervical Cancer: 2008[cited 2011 December 4]. Available from: http:// www.medicalnewstoday.com/releases/100749.php. 8. Schiffman, Mark and Philip E.Castle. Human Papillomavirus: Epidemiology and Public Health. Archives of Pathology & Laboratory Medicine. 2003 Aug; 217 (8): 930-934. 9. The lesions are hole-like cuts in the epithelium of cervical cells that allow for oncogenic HPV cells to enter and cause them to proliferate uncontrollably, leading to malignant tumors. 10. Ojcius, David et al. Can Chlamydia be stopped? Scientific American, 2005 May; 72-79. 11. WebMD [Internet]. Sexual Conditions Health Center: 2010 [cited 2011 October 27]. Available from: http://www.webmd.com/sexual-conditions/chlamydia-tests. 12. EmedTV [Internet]. Chlamydia Treatment: 2006 [cited 2011 October 26]. Available from: http://chlamydia.emedtv.com/chlamydia/chlamydia-treatment.html. 13. American Cancer Society [Internet]. Cervical Cancer: 2010 [cited 2011 November 1]. Available from: http://www.cancer.org/Cancer/CervicalCancer/DetailedGuide/

Book 1.indb 19

Sami Ismail is a senior at the University of Chicago majoring in Anthropology on the pre-medical track.

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UCHICAGO

Top and Bottom or Truth and Beauty? Science’s Languishing Horizontal Dimension and Why it Needs to be Fostered Tyler Lutz

n the 1960’s, when quark research was still in its infancy, the two sub-nuclear particles today called the top and bottom quarks were better known by the provisional and unapologetically whimsical monikers of “truth” and “beauty.” Yet by the time the former of these two particles was confirmed to exist in 1995, “truth” and “beauty” had been discarded for their admittedly more formalsounding counterparts, “top” and “bottom” [1]. Did science lose anything in the process? On the surface, it’s a petty question; no matter how much effort might be expended quibbling over conventional nomenclature, all the interesting science contained in quarks will be the same regardless of the names we slap on the particles—the universe simply does not care about the nominal difference between a “top” quark and a “hippopotamus” quark for that matter. But let’s rephrase the question: did science lose anything in the process, where science is taken in a second sense to denote not some formal body of knowledge of what makes reality tick, but more generally the organized human pursuit of knowledge? Again, the answer is likely a firm no. Aside from disappointing the more playful at heart, scientific research today is as robust as it would have been had we kept “truth” and “beauty.” What the naming shift does offer, however, is a profound metaphor for a process operating just under the surface of science, a systematic shift away from thinking about the truth and beauty of science and instead a privileging of its top and bottom. And it is this shift which could constitute a significant loss to science, both as a body of knowledge and as a human pursuit. In one sense, “top” and “bottom” were not invented by particle physicists—they’ve been integral constituents of science since the ancient Greek philosophers’ musings on the need for objective, causally explanatory reasons for events. In

20 THE TRIPLE HELIX Spring 2012 Book 1.indb 20

doing so, the Greeks broke the ground for science’s bottom, its sturdy foundation of knowledge coupled with predictive models, upon which its top, the fortified edifice of human technology, would gradually be built [2]. These two directions collectively form the axis around which modern science revolves, surviving today in the much discussed distinction between ‘theory’ and ‘practice’ in science. But if modern-day science consists of little more than an elaboration of two distinct questions – why things are the way they are and how we can use this to our advantage – should it necessarily be left at that? Or might we expect another ‘scientific revolution’ to be looming on the horizon? Reproduced from [8] We’re not flirting here with historical speculation; what we want is either an assurance that science, in its modern conception, is realizing its fullest potential or, if not, at least a sense of what it is lacking. For a possible answer, we turn back to quarks. What ever happened to ‘truth’ and ‘beauty?’ Asserting the centrality of truth in science seems as incontrovertible as asserting the usefulness of engineering; at least at the level of colloquial parlance, science is truth (Lat. scientia = knowledge) [3]. It is a comforting thought, but unfortunately not one that holds up to the facts gleaned from even the most cursory glance at the history of science. Science has rarely, if ever, been wholly true; the merciless barrage of new data and ideas to which science has been subjected has forced scientists to be constantly prepared to tweak, extend, or outright dispose of existing theories. In what can only be called recent history, the earth has gone from the center of the universe to a humble satellite whizzing around the sun (the universe’s ‘true’ center), and finally to an utterly insignificant chunk of rock suspended somewhere in a universe with no center in the first place [4]. Something as ostensibly intuitive as translational motion has been persistently re-imagined from Aristotle’s concept of a dance around an eternal static

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UCHICAGO mean to Newton’s deterministic interplay of forces and inertial masses, then to a conceptually profound relativistic scheme due to Einstein. And that’s not even to mention quantum mechanics’s computationally intimidating probabilistic wave function transformations. One might reasonably contend: So what if science misses the mark every now and then or becomes mired in empirical inexactitudes—must we now resort to a nihilistic rejection of science altogether? In its unwavering quest to delve into a deeper understanding of reality, science can find consolation in approximate knowledge: truth which, if perhaps not universally comprehensive and immutable, is at least consistent with experiments at the threshold of precision possible in a given time period. Science can still be a quest for truth even if truth itself, like beauty in art, may assume vastly disparate meanings depending on historical context.

What we want is either an assurance that science, in its modern conception, is realizing its fullest potential or, if not, at least a sense of what it’s lacking Thus equipped with a functional conception of truth at its core, our science-as-truth can now progress to its more pragmatic existence at the heart of human technology. The criterion of empirical consistency maximizes the predictive prowess of natural philosophy; there is nothing fundamentally untrue about labeling the earth as a static “center of the universe”, but doing so cripplingly obfuscates our models of the trajectories of other bodies. This exemplifies many of the paradigm shifts that the corpus of scientific knowledge underwent between the sixteenth and nineteenth centuries (echoing here historian Thomas Kuhn’s Structure of Scientific Revolutions) [5]. Given the necessary bounds on truth possible in his time, Aristotle’s static-seeking inertial conception of movement was not wrong per se, but it simply did not have as extensive a predictive power as Newton’s. Thus, enter modern science-as-truth: a collection of coherent propositions which provide causal explanations for observed phenomena coupled with maximized predictive functionality. Science produces the primitive raw materials used to build the twenty-first century Tower of Babel, with its technological bulwark, bolstered by ever deeper foundations, stretching towards god-like omnipotence (we are reminded of Oppenheimer’s reference to Vishnu on the occasion of the first successful test of nuclear weapons: ‘’Now I am become death, the destroyer of worlds’’). And beauty? A strictly truthdriven science forces beauty into the back seat. What we’ve constructed here is the conventional scienceas-truth, which, though apparently stable when seen from a distance, may rest on a theoretical quagmire: How can one be

Book 1.indb 21

confident of the uniqueness of truth? Even if different causal circumstances might lead to the same outcome – say matter arising from atoms on one hand or from combinations of air, earth, wind, and fire on the other – science seems to have its compass set on isolating one as the ultimate cause of the phenomenon. Although this assumption may make sense in biology or chemistry, in which few would be amenable to positing the existence of multiple disparate but logically equivalent underlying realities, is it really warranted in physics, the gateway through which all truth enters science? Answer: no, both at the microscopic level of everyday science and in terms of grander conceptions of the progress of science as a whole. The truths out of which we have just alleged all science to be built fall into a continuum with unexceptional truths at one pole and beauty at the other, an axis perpendicular to the vertical ‘top’ and ‘bottom’ from above, yet indeed in every way as essential to science. At times, beauty does more than just come along for the ride; more often than not, it is sitting in the driver’s seat. The volatile and historically contingent nature of the “truth” of scientific discoveries as adumbrated above automatically reduces any science too rigidly focused on attaining instant truth to one with few real prospects indeed; revolutionary science rarely progresses by expounding upon existing truths or, as in mathematics, by moving up a ladder of indisputable logical truths to arrive at a grander truth. It advances rather by stepping out on a branch, by proposing and testing ideas that, though most likely doomed to fail, might actually lead one to another branch of truth. That is to say, at least in the everyday life of science, an entirely new dimension needs to be introduced: instead of merely building upon and towards new truths, science must also pursue beautiful propositions in the hopes that they may one day be confirmed true. Historically important examples of this process include both Einstein’s flagrantly counterintuitive conflation of space-time and quantum mechanics’s still more fancifully absurd assertion of the fundamentally probabilistic nature of such elementary properties as locality and velocity.

At times, beauty does more than just come along for the ride; more often than not it is sitting in the driver’s seat

Science is and indeed must be willing on occasion to chase ideas for mere beauty rather than out of an incessant demand for rigid truth. But are such methodological considerations the only places where beauty comes into play? Imagine an iceberg. Though there exist laws governing how icebergs form and how the shape of the iceberg will dictate which part of it peeks out above the surface and which parts

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UCHICAGO remain submerged, merely looking at the tip of the iceberg does not unambiguously specify the shape of the submerged portion. The best we can do is draft up a few ideas about what might be lurking beneath the water’s opaque surface and test which ideas float and which ones sink. What has just been described here is the heart of the scientific method: recognition of a precise problem in the world, logical drafting of reasonable hypotheses, and finally rigorous testing of these hypotheses. And, lo and behold, it works—at least in disciplines in which it is possible to probe deeper and perceive the underlying shapes, either directly or more obliquely. But what if this is impossible, at least in the foreseeable future? What if the surface of the water is frozen over such that probing the base of the iceberg would be impossible?

Unlike many other ‘breakthroughs’ in science, Lagrange didn’t introduce anything fundamentally new; his results...were fully consistent with Newton’s original conception

The latter situation is often the one faced by modern-day physicists; the biggest objection fielded against string theory, for instance, is not that it lacks conceptual depth or beauty, but rather simply that we do not and perhaps never will have the proper apparatus to conclusively test it. To the naysayers this means drop the idea until it can be put on more solid footing. But perhaps a better argument is to be found in positing that, as long as an idea is consistent with what we can observe and offers conceptual power, we have no grounds to reject it. Consider the principles behind classical conceptions of motion: Newton’s three equations fully constrain motion in almost all physically relevant circumstances by explaining motion as an interplay between inertial masses and forces that generate acceleration. In principle, classical mechanics was thereby completed, as all that remained was to elaborate the minutiae of planetary movement. But somehow the story did not end there; in 1788, Joseph-Louis Lagrange radically recast classical mechanics by centering it around trajectories

that minimize energy [6]. The fascinating part is that, unlike many other ‘breakthroughs’ in science, Lagrange did not introduce anything fundamentally new. His results, though assuming a substantially different underlying reality, were fully consistent with Newton’s original conception. Lagrange, through some fancy mathematical footwork, was thus able to create a parallel truth to Newton’s reality. This development is certainly not a unique event, even in the relatively narrow study of translational motion. One of Richard Feynman’s many enduring contributions to science was his development of the path integral approach to movement in the quantum realm, which effectively describes motion as a consequence of averaging over all possible paths a particle can take. Though again fully equivalent with existing data and models, this recasting opened up many facets of quantum mechanics for more rigorous investigation [7]. But as much potential as such parallel approaches might have, their development is often systematically discriminated against, if not in the laboratory, then certainly in the introductory science classroom. Naturally, conceding the possibility of parallel truths seems a little like admitting defeat. But in any case, we have no logical motivation to assume the uniqueness of truth, when, as the above examples demonstrate, simultaneous parallel conceptions of truth often bring us much closer to a single unified picture by providing us with greater depth in understanding such seemingly elementary phenomena as motion. Science will always have a top and a bottom. Science’s power to probe into the underlying nature of reality fulfills a fundamental human need, and it would be ridiculous to wholly disregard the technology that can be developed from this understanding. Science’s other pole cannot, however, be taken for granted. Without support for the types of creativity and imagination that underlie potentially paradigm-changing ideas, science will, at best, fail to realize its explanatory and creative potential or, at worst, confine itself in a stalemate in which no substantive advances are possible. This entails a certain amount of risk, of course, when full mathematical and empirical rigor have not had the chance to catch up. It is, however, a risk which must be taken. Science may have lost little by standing behind ‘top’ and ‘bottom,’ but it will almost certainly flounder if it fails to understand the nuanced continuum of the roles that both ‘truth’ and ‘beauty’ have to play. Tyler Lutz is a third year at the University of Chicago, double majoring in Physics and English.

References: 1. Physicists Discover Top Quark (Fermilab News Release) [internet]. Batavia, IL: Fermilab Office of Public Affairs; 1995 Mar 2 [updated 2001 Feb 26; cited 2011 June 25]. Available from: http://www.fnal.gov/pub/inquiring/physics/discoveries/pr/ top_news_release.html 2. Encyclopedia Britannica. Aristotle [Internet]. [Place unknown]: 2011 [cited 2011 June 25]. Available from: http://www.britannica.com/EBchecked/topic/34560/ Aristotle 3. Oxford English Dictionary. Science [internet]. Oxford, U.K.: Oxford University Press; 1989 [updated 2011 June; Cited 2011 June]. Available from: http://www.oed. com/view/Entry/172672redirectedFrom=science#eid

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4. Gibbs, Philip. Where is the centre of the universe? [internet]. [Place unknown]: 1997 [cited 2011 June 25]. Available from: http://www.desy.de/user/projects/Physics/ Relativity/GR/centre.html 5. Kuhn, Thomas S. The Structure of Scientific Revolutions. Chicago: The University of Chicago Press; 1962. 6. Lagrange, Joseph-Louis. Mécanique Analytique. Paris: Ve Courcier; 1788. 7. Murayama, Hitoshi. Feynman’s Path Integral Formulation [internet]. Berkeley: 2006 [cited 2011 June]. Available from: http://hitoshi.berkeley.edu/221A/pathintegral. pdf 8. http://www.ibiblio.org/wm/paint/auth/bruegel/littlebabel.jpg

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UCHICAGO

Healthcare Reforms: The Eagle and the Dragon Frank Qian

he Eagle. The Dragon. In recent years, the economic prowess of the United States and China has been solidified at the top ranks of the world, with GDP growing at 2.8% and 10.3%, respectively and comprising nearly 40% of the entire world. The populations of the two nations are even more astonishing, encompassing nearly a quarter of the entire world’s people. Despite economic prosperity, both nations are facing challenges to provide affordable yet high-quality health care to all citizens [1, 2]. While health care expenditures are much higher in the United States than in many other developed countries and the share of Gross Domestic Product (GDP) devoted to health care spending in the U.S. is more than 17% [3], approximately 50 million Americans are uninsured [4]. In the past decades, China has abandoned its socialist model in favor of Western-style privatized medicine, while the government slashed funding for public hospitals. As a result, millions of uninsured and poor Chinese may face bankruptcy due to a serious illness [5]. One common challenge that both US and China Reproduced from [27] are facing is geographic disparities in the availability and quality of healthcare [6, 7]. Geographic inequalities in healthcare reveal fundamental flaws within resource allocation as well as shed light on potential directions for further reform such as in the distribution of healthcare spending and workforce allocation. In both nations, the geographic variations in the spending on healthcare expose fundamental differences in quality and accessibility. A key healthcare quality gauge is given by per capita healthcare spending or the amount of income spent per individual on healthcare [8]. In the U. S., where healthcare spending is frequently criticized as inefficient and even wasteful by media outlets, large gaps in per capita healthcare spending between regions may be a contributing factor. For instance, a study conducted by the National Health Statistics Group in 2004 measured the per capita spending on healthcare for all fifty states which ranged from $3,972 in Utah to $8,295 in the District of Columbia [6, 9]. These statewide variations are magnified further across entire regional districts as shown by a study in 2005 [10]. On average, a state in the Rocky Mountain area will receive only approximately half the Medicare funding compared to a state in the Northeast or Pacific Coast. The latest data from © 2012, The Triple Helix, Inc. All rights reserved.

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the U.S. Congressional Budget Office indicate that in recent years, geographic variation in healthcare spending has been steadily increasing. A portion of this discrepancy, however, is due to changes in income and spending patterns across regions [10]. For states that rely heavily on manufacturing as sources of revenue, offshoring of these industries to locations outside of U.S. have heavily impacted the employment and income for residents of these states. Nevertheless, inaccessibility to or lack of high-quality treatments likely contributes more to lower per capita healthcare spending in the Rocky Mountain regions or Southeast [10]. Wide geographic variation in healthcare spending may inhibit the initiation of universal healthcare in the U.S. and result in disproportionate morbidity/mortality rates in disadvantaged states. Even worse, these discrepancies could prevent a possible national endeavor for quality evaluation of medical care. China similarly sees large geographic variations in healthcare spending, particularly exhibiting patterns of inequality progressing from East to West. Since China adopted a market economic policy in 1978, the Chinese government has initiated budget cuts for public hospitals; meanwhile, the responsibility of funding for healthcare shifted from the central government to private companies [11]. A new healthcare model based mainly on private practice drastically increased patient out-of-pocket payments for physician consultations and medication. In turn, different economic growth rates began to signify enormous inequalities in the degrees of development in medical care facilities and financing across the geographic boundaries of China. In 2008, Jiangsu province, located on the Eastern seaboard of China, had an average per capita healthcare spending of ¥186 RMB (≈$29.33 USD) [12], compared to ¥143 RMB (≈$22.55 USD) in Henan Province (Central China) and merely ¥56 RMB (≈$8.83 USD) in Inner Mongolia (Northwestern China). China’s continual urbanization will enlarge these economic gaps until its expected completion in 2030 [13]. In the short-run, however, simple developments in medical facilities may not solve the imbalance in healthcare spending between the affluent East and the impoverished West. In disadvantaged regions, patients may simply decide to avoid THE TRIPLE HELIX Spring 2012 23 3/29/2012 7:56:55 PM

CMU UCHICAGO seeking out medical services despite its availability. In a 2006 In China, where a sharp economic distinction still exists New York Times report, 36-year old Jin Guilian, who was between the urban East and the rural West, a disproportionate suffering from a severe cardiac condition at the time, was distribution of the healthcare workforce naturally arises [20] forced to embark upon a nearly 500 mile long journey from from the large geographic disparity in per capita health care Guangdong in Southern China to Fuyang, Anhui in order to spending. The 2006 Health Statistics Annual Report shows the seek out affordable medical care [14]. Many such cases oc- number of healthcare workers per one thousand population cur every day across poverty-stricken areas of China while as 4.66 in the Eastern Region, 4.15 in the Central Region, and other patients fully neglect treatable diseases, magnifying a mere 3.70 in the Western Region [20]. Western provinces unnecessary mortality rates. Yang Yunbiao, a member of a of China are historically underserved in terms of healthcare Chinese NGO that aids disadvantaged patients writes that personnel and lack proper medical facilities. The collapse “there is basically no safety net at all for medical care in the of the “barefoot doctors” primary care system in the early village I live in… [people] just staying at home in bed without 1980s further exacerbated the shortage of medical personnel treatment” [14]. From these examples, it is clear that regional in the rural areas of Western China [13]. Previously, peasants disparities in medical care have led to a fundamental disuse who received basic medical training worked as primary care of the healthcare system in China which may need the help physicians in rural clinics and provided preventive care and of social organizations and the improvement of the quality treatments with traditional herbal medicine for little to no of life as a whole to compensate. cost. However, with the economic reforms of the 1980s, the The distribution of healthcare workers, particularly transformation of the Chinese healthcare system from having physicians (also includes, nurses, medical technologists, and a preventive focus to becoming more treatment-oriented have administrative staff), by region is perhaps the greatest con- seen costs skyrocket, particularly for urban medical centers. tributing factor to the regional With continual urbanization and disparities seen in the U.S. and improved education of a new China. According to 2006 U.S. generation of Chinese citizens, Wide geographic variations Census Bureau data, the number living styles among rural populaof primary care physicians per tions are also beginning to more in healthcare spending 100,000 population ranges widely, closely mimic urban populations may potentially inhibit from 462 in Massachusetts to 169 [8]. Previously strong distaste for in Idaho [15]. This disparity in the Western medicine has now been the initiation of universal availability of healthcare personreplaced with immense preferhealthcare in the U.S. and nel suggests that large numbers to ence for medicine that relies on be deprived of medical care even advanced technology and pharresult in disproportionate for diseases such as the flu, arthrimaceutical products. This trend morbidity/mortality rates in tis, or asthma [16]. Another key in turn rendered “barefoot docproblem is the general decrease tors” economically infeasible [13]. disadvantaged states of primary care physicians and Moreover, resistance to economic sharp increase in the number of and infrastructural developments specialized physicians [17]. For from minority ethnicities such most aspiring physicians, pursuing a specialty may mean a as Tibetans and Uighurs may inhibit advancements in quality few additional years of training but is often rewarded with a and accessibility of healthcare in Western China [21]. If the higher starting salary and a less stressful work environment gap is not closed between the number of health workers avail[18]. This in turn leads a disproportionate number of medical able in Eastern and Western China, the creation of a unified graduates to pursue careers in prominent medical centers in healthcare system may prove nearly impossible. the Northeast or Pacific Coast where job opportunities and Fundamental inequalities in healthcare resources and fully-equipped facilities are more readily available. Meanwhile, availability will prove difficult to fully abolish due to inherent much of the Northwest and Southeast remain underserved differences in income levels for patient populations and career in the number of health workers, particularly primary care opportunities for healthcare workers. Yet minimizing the geophysicians, where fewer resources and job opportunities are graphic gap in healthcare spending and availability of services presented [17]. To account for this problem, it may prove will be key to a more efficient and reliable healthcare system. beneficial for medical schools or governmental agencies to In the United States, medical facilities known as the Federally offer incentives for students to pursue primary care. According Qualified Health Centers (FQHCs) are beginning to augment to the March 2010 Patient Protection and Affordable Care Act healthcare provisions served by regional hospitals and medi(ACA), certain primary care services are now to be awarded a cal centers [16]. These health centers provide a general means 10% bonus payment from Medicare [19]. Moreover, prominent of preventative and primary care to families in low-income medical colleges, such as Harvard and Duke, are expanding and rural areas as well as referrals to specialty hospitals. In their primary care fellowships to provide students additional 2009, the New York Times documented the effectiveness of monetary aid, which may help alleviate their financial burdens FQHCs in the rural town of Plainfield, Vermont where primary after graduation. care was no longer a pressing issue for many disadvantaged

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UCHICAGO families [22]. Plainfield resident Kathleen Hoyne noted the in medical school debts and tax benefits. The efforts on behalf importance of the clinics to their children’s well-being: “This of the FQHC may diminish the large geographic healthcare place is so important. Neither my husband nor I have health disparities in the U.S., particularly targeting areas with large migrant/seasonal populations [23]. insurance through work.” In China, the New Rural Cooperative Medical Care In addition, FQHCs tend to better suit the specific cultural and economic settings of a community than a general hospital and System (NRCMCS), begun in 2005, is starting to provide more affordable healthcare to hence attract a greater number of rural populations, particularly patients who may have otherwise in Western areas of China [11]. chosen to neglect medical care. In disadvantaged regions, Under this system, a medical Community health centers can coverage of ¥50 RMB (~US$7), also offer services to uninsured patients may simply with ¥40 RMB supplied by the and older adult populations, decide to avoid seeking out central and provincial governwhich may prove helpful in ments and ¥10 RMB by the indikeeping Medicare more sustainmedical services despite its vidual patient, will be allotted to able. Undoubtedly, only time will availability each enrolling individual. Besides tell whether or not FQHCs can successfully deliver medical care relieving the pressures on large while retaining their low-cost and urban hospitals, NRCMCS will low-profit model. Moreover, physicians and hospitals provid- also offer more career opportunities for health graduates at ing medical services in disadvantaged or rural areas [16, 23] the township and village level clinics [24]. This measure will are offered additional encouragement, including reductions direct more steady traffic of patient cases to the lower tiers Reproduced from [28]

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CMU UCHICAGO of the Chinese healthcare system, providing the economic incentive for rural physicians to continue their practices. So far, these measures have greatly diminished the convenience and monetary barriers that prevented many disadvantaged individuals in rural areas from seeking out proper medical care. At the same time, governmental agencies and NGOs are providing financial assistance to medical graduates to serve in disadvantaged or rural hospitals [25]. Monetary aids aim to furnish practicing health workers with higher living standards and ensure that they have continuing career opportunities once they leave the rural clinics. Such methods among others will be imperative to an improved distribution of healthcare workers across China. Despite governmental and private efforts at healthcare reforms in the United States and China, provision of highquality and accessible universal healthcare in the two nations will prove to be a persistent challenge. Besides addressing the geographic disparities, a general lack of qualified physicians and nursing staff as well as continual measures for medical quality still demand resolutions, such as more physicians attending to patients in disadvantaged areas. At the same time, NGOs and society as a whole could also contribute their unique roles through advocacy work and general awareness. While these two nations are looked upon by countless others for their economic success, the United States and China will certainly benefit from observing successful healthcare models in other developed nations. The healthcare systems of Japan and Canada are both funded by universal taxpayers and strictly References 1. Roehr, B. (2008). “Health care in US ranks lowest among developed countries, commonwealth fund study shows.” BMJ, 337(a889). 2. Brown, J. (2011, April 14). “China struggles with health care reform amid growing demand.” PBS News Hour. Available at: http://www.pbs.org/newshour/bb/health/ jan-june11/china_04-14.html (Accessed on 30 January 2012). 3. Centers for Medicare & Medicaid Services (2009). National Health Expenditure Data. Available at: https://www.cms.gov/NationalHealthExpendData/25_NHE_Fact_ Sheet.asp. (Accessed on January 30, 2012). 4. U.S. Department of Health and Human Services (2011). Overview of the Uninsured in the United States: A Summary of the 2011 Current Population Survey. Available at: http://aspe.hhs.gov/health/reports/2011/CPSHealthIns2011/ib.shtml (Accessed on 30 January 2012). 5. Ma, J., Lu, M., & Quan, H. (2008). From a national, centrally planned health system to a system based on the market: lessons from China. Health Affaires (Millwood), 27(4):937-48. 6. Dartmouth University (2011). The Dartmouth Atlas of Health Care. Available at: http://www.dartmouthatlas.org/data/region/ (Accessed on January 30, 2012). 7. MOH (2009). China’s Health Statistics Yearbook 2009. Ministry of Health of the People’s Republic of China. 8. Baicker, K. Chandra, A. & Skinner, J.S. (2005). “Geographic variation in health care and the problem of measuring racial disparities.” Perspectives in Biology and Medicine, 48(1 Suppl):S42-53. 9. National Health Statistics Group (2007). Health care expenditures per capita by state of residence, 2004. Available at: http://shfonew.kff.org/comparemaptable.jsp?yr =14&typ=4&ind=596&cat=5&sub=143 (Accessed on 30 January, 2012) 10. Orszag, P. R. Congress of the United States, Congressional Budget Office. (2008). Geographic variation in health care spending. Available at: http://www.cbo. gov/ftpdocs/89xx/doc8972/02-15-GeogHealth.pdf (Accessed on 30 January 2012). 11. Hsiao, W. C. Disparity in health: The underbelly of China’s economic development. Informally published manuscript, Harvard University School of Public Health, Cambridge, MA. Available at: http://www.hsph.harvard.edu/health-carefinancing/files/harvard_china_review_-_rmhc.pdf (Accessed on 30 January 2012). 12. Brixi, H. Mu, Y. Targa, B. et al. (2011). Equity and public governance in health system reform: challenges and opportunities for China (5530). East Asia and Pacific Region: The World Bank. 13. Chu, D. S. (1984). “Demography, population growth, and population policy in China: a brief history from 1940 to the present.” Chinese Sociology & Anthropology 16(3-4): 1-42. 14. French, H. W. (2006, January 16). Wealth grows, but health care withers in China.

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Another key problem is the general decrease of primary care physicians and sharp increase in the number of specialized physicians controlled for medical and administrative spending. In turn, healthcare packages in these nations provide equivalent or greater benefits at only a fraction of the cost compared to the U.S. and China. Both the U.S. and China are proposing to offer universal healthcare by 2020. It is a paramount but feasible goal. The Eagle and the Dragon simply have to look to their neighbors and see what experiences they have to offer. Frank Qian is a second year undergraduate student studying Biological Sciences with a minor in Statistics. He is interested in health policy and its effects on public health and medical practice.

The New York Times. Available at: http://www.nytimes.com/2006/01/14/ international/asia/14health.html?pagewanted=all (Accessed on 30 January 2012). 15. U.S. Census Bureau (2006). Medical personnel rankings by state in the United States. (2006). Available at: http://www.census.gov/statab/ranks/rank18.html (Accessed on 30 January 2012). 16. National Association of Community Health Centers. (2007). Access denied: A look at America’s medically disenfranchised. Available at: http://www.graham-center.org/ PreBuilt/Access_Denied.pdf (Accessed on 30 January 2012). 17. Lakhan, S. E. & Laird, C. (2009). Addressing the primary care physician shortage in an evolving medical workforce. International Archives of Medicine, 2(1):14. 18. Mark Linzer, M.D., Linda Baier Manwell, M.S., Eric S. Williams, Ph.D., et al. (2009) “Working conditions in primary care: Physician reactions and care quality,” Annals of Internal Medicine 151(1), pp. 28-36. 19. American College of Physicians. Medicare primary care bonus payment program. Available at: http://www.acponline.org/running_practice/practice_management/ payment_coding/bonus.htm (Accessed on 30 January 2012). 20. Chou, W.L. & Wang, Z. (2009). “Regional inequality in China’s health care expenditures.” HealthEconomics, 18 Suppl 2:S137-46. 21. Ang, A. (2009, July 06). Xinjiang riots echo last year’s Tibet unrest. The Seattle Times. Available at: http://seattletimes.nwsource.com/html/nationworld/2009424300_ apaschinarestlesswest.html (Accessed on 30 January 2012). 22. Herbert, B. (2009, Aug 19). Hard to believe!. New York Times. Available at: http://www.nytimes.com/2009/08/15/opinion/15herbert.html (Accessed on 30 January 2012). 23. House Committees on Ways and Means, Energy and Commerce, and Education and Labor (2010). Health insurance reform at a glance rural America. Available at: http://docs.house.gov/energycommerce/RURAL.pdf (Accessed on 30 January 2012). 24. Zhang, H. (2007, July 19). Health workforce development on the primary health care in rural China. Presentation delivered at Ministry of Health of the People’s Republic of China: Health human resources development center exchange, Beijing, China. 25. Zhou, Y.Y., & Wang, L.J. (2007). Some suggestions for solving human resource problems in China rural hospitals. Modern Preventive Medicine, 34 (8): 1514-17. 26. NC Health Plans. Photograph retrieved from <http://www.nchealthplans.com/ news/category/health-care-reform/> 27. Solar Feeds News and Commentary. Photograph retrieved from <http://www. solarfeeds.com/how-the-u-s-should-beat-china-in-solar/usa-china-flag-puzzle/> 28. FQHCs Map. [Image on the Internet] 2010 [cited 4 March 2012]. Available from: http://www.raconline.org/racmaps/mapfiles/fqhc.png

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UCHICAGO

Acupuncture: A Needling Medical Mystery Talia Retter

gloved hand strikes a needle through the bared skin of the victim… patient. There is no crime, but it is an intriguing mystery, containing multiple culprits, chase scenes, and the hope of capture and conviction. A medical mystery, in the form of a cure that is not yet understood, has countless lives at stake: by solving this case, we may make leaps in scientific knowledge and medical application. Acupuncture is indeed a needling mystery: both the biological mechanisms of its effects and its relevant applications are still unclear to Western science. Yet, every good mystery has a twist. In the case of acupuncture, it is that the case has been buried for hundreds of years because of the difficulty of researching acupuncture according to the scientific method and the complexity of integrating Eastern and Western practices. Only in about the last two decades has research in acupuncture been seriously taken up by Western medicine (C. Yuan, 2012).

In the last two decades, the mystery of acupuncture has pricked the interest of Western science… First, the case history: an examination of acupuncture. In its adoption into Western medicine, acupuncture involves the nearly painless insertion of thin needles into three to ten of the hundreds of acupoints, specific points on the body lying over arteries, nerves, or lymph passageways. Needles typically remain inserted for about ten to twenty minutes, and may cause “feelings of tingling, numbness, warmth, or aching” [1]. While inserted, needles may remain motionless, be twirled, or be paired with electrical inputs. The FDA approved acupuncture needles for use by licensed practitioners in 1996, provided that the needles are sterilized and labeled for single use only, and acupuncture may be covered by medical insurance; the advertised price range for a single acupuncture session is around $50-150, making it a relatively very inexpensive medical practice. There are few reasons to exclude anyone from receiving acupuncture, and side effects are uncommon, but may include minor bleeding in about 10% of patients and, extremely rarely, infection and injury to vital organs if needles are inserted too deeply [2]. The motive for researching acupuncture is quite apparent: acupuncture has been shown to have many potential health benefits. Acupuncture has proven most beneficial in three © 2012, The Triple Helix, Inc. All rights reserved.

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cases: reducing pain, especially chronic pain from arthritis or joint pain, decreasing vomiting and nausea after surgery or chemotherapy, and alleviating depression during pregnancy. The list of less researched potential benefits of acupuncture is lengthy, and includes treatment for physiological disorders, e.g. high blood pressure, digestion, and facial aging, as well as more complex or psychological issues, e.g. asthma, anxiety, fatigue, and infertility. Western science is investigating a lineup of nine main reasons for how acupuncture works: hormones/neurotransmitters, opioids, blood flow, bioelectricity, the pain gate, inhibitory controls, complex cortical processing, patient belief, and patient involvement. The first four suspects listed focus on the cellular and molecular level. Hormones and neurotransmitters pose a possible explanation, because when an acupuncture needle is inserted, pressure increases in the skin, which may be picked up by sensory mechanoreceptors, which in turn signal to nerves, and thus transmit signals from the periphery to the brain. Activation of the cranial vagus nerve, a prominent nerve extending into

Reproduced from [9]

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UCHICAGO the brain, leads to increased serotonin levels and decreased benefits of acupuncture. cortisol levels, which is linked to increased pleasure and deDespite this complexity, the current investigation is hot on creased stress [1]. acupuncture’s tracks. In the last two decades, the mystery of Another theory targets endogenous opiods, a class of acupuncture has pricked the interest of Western science, with a neurotransmitters including endorphins and enkephalins. leap from about 800 articles on acupuncture published in 1990 The concentrations of opiods increase in the body following to over 2,500 articles in 2010 [6]. For an example of successful acupuncture, and these substances have analgesic, or painkill- research in acupuncture, one study at the Martinos Center at ing, properties [1]. Alternatively, changes in blood flow may the Massachusetts General Hospital in Boston concluded that be responsible. An increase in blood flow stimulated by the patients with fibromyalgia, a chronic pain disorder, show needles may increase oxygen flow and amounts of immuno- increased endorphin levels from real and sham acupuncture, logical cells at the needle sites [2]. Yet again, bioelectricity but only real acupuncture causes an increased number of painmay be the primary reason, since acupuncture needles increase reducing neurotransmitter receptors, thus causing decreased skin conductance, a measurable electrical voltage produced pain over longer periods of time [2]. As concluded by the by the very small, endogenous flow of electricity in the skin, National Institutes of Health (NIH) Consensus in 1997, Western the increase of which may increase healing [3]. mechanisms that explain the beneficial effects of acupuncture One of the two theories targeting sensory neurons is are beginning to be discovered, a fact that is “encouraging and the “pain gate” theory, which asserts that nerve signals from may provide novel insights into neural, endocrine, and other acupuncture sent along myelinphysiological processes” [5]. The ated axons may cause a sensory NIH thus suggests that further “gate” in the spinal cord, at a research in acupuncture would be As concluded by the NIH location called the substantia advantageous and manifest in digelatinosa, to close, thus blockrect improvements in healthcare. Consensus in 1997, Western ing slow pain signals traveling This mystery investigation mechanisms that explain the along unmyelinated axons from of acupuncture may seem intrigupassing up the spinal cord and ing and fast-paced, but in fact effects of acupuncture are being processed by the brain [3]. acupuncture has existed for over beginning to be discovered, a However, as suggested in the diftwo thousand years in China [3]. fuse noxious inhibitory controls Acupuncture gained inclusion fact that is “encouraging and (DNIC) theory, acupuncture may in Western society just over two may provide novel insights into activate neurons, which typically hundred years ago, from celebsignal for pain, and although not rity endorsement more than scineural, endocrine, and other perceived as pain by the patient, ence. Acupuncture was brought physiological processes” [5] “reboot the automatic nervous to the United States in 1825 by system” and eliminate lingering Ben Franklin’s grandson, and pain sensations, as practitioner was popularized in the sevenAlejandro Elorriaga asserts [2]. ties by actor James Reston, after The remaining theories of how acupuncture works concern President Nixon increased good relations between the United the brain and psychology. Dr. Vitaly Napadow, an acupuncturist States and China through diplomatic travels [1]. But despite and Ph.D., comments that ‘’acupuncture affects many systems their long acquaintance, Western science and acupuncture in the body, including parts of the brain that are involved with have little understanding. Instead of being fully integrated processing emotion and pain” [4]. Neuroimaging studies have into Western medicine, acupuncture is viewed as an alternashown that “acupuncture affects a network of systems in the tive, “evidence-based medicine,” validated primarily by the brain, including decreasing activity in the limbic system, the evidence of its beneficial practice instead of an understanding emotional part of the brain” [2]. Furthermore, the placebo of how it works, and it is classified as a traditional Chinese effect may be present, enabling the patients’ expectations to medicine, or a complimentary and alternative medicine. play a part in why acupuncture is so efficacious. So why has acupuncture historically not been researched Alternatively, increased involvement of patients in their more in Western science? Firstly, acupuncture has been difficult own healthcare may be the target of investigation: although to research using the scientific method because researchers acupuncture is often recommended to patients by their general have had problems creating a good control group to which practitioners, the choice to pursue it or not, and the exercise of the effects of acupuncture can be compared. Control groups going for the treatment, may make patients feel more in control are essential in the scientific method because they allow of their health decisions and lives: “‘In general in integrative experimental manipulation that can eliminate confounding medicine, when patients are involved in their healing process, variables such as placebo effects from anticipated treatment. they have a tendency to do better,” reflects Angela Johnson, Unlike a drug study, when a placebo pill can be used, it is a practitioner at Rush Children’s Hospital [5]. The depth of challenging to come up with a method for “fake acupuncture,” the mystery is great, because any or all of these proposed since the insertion of acupuncture needles is, quite imaginably, mechanisms may be working together to produce the medical distinctive. Furthermore, the parameters required for valid

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UCHICAGO sham acupuncture are undefined, since the mechanism for how acupuncture works is still unclear. Methods for sham acupuncture that have been implemented, with uncertain effectiveness, include less deep insertion of needles, insertion of needles not in acupoints, and fake electrical stimulation with un-inserted needles. To avoid the problem of creating a suitable control, some researchers have compared acupuncture to validated medications. In one study at the Henry Ford Health System, conducted by Dr. Eleanor M. Walker, researchers compared acupuncture to a drug, Effexor, regarding treatment of hot flashes in cancer patients, and found acupuncture to be equally as effective and with fewer side effects. The benefits of acu-

Dr. Vitaly Napadow, an acupuncturist and Ph.D., comments that ‘’acupuncture affects many systems in the body, including parts of the brain that are involved with processing emotion and pain” [4]

puncture treatment are not merely temporary: “it lasts,” says Dr. Walker, “and the placebo effect doesn’t last once you stop a treatment’’ [7]. Other studies use animals as subjects, which are unlikely to have psychological expectations of benefiting from acupuncture. And as neuroimaging and microscopy progress, the structure and activity pathways of neurons in the periphery and brain become better understood, making acupuncture research increasingly accessible. The inability to have a consistent, valid control in the past has limited the validity and robustness of studies on acupuncture; however, this limitation has been alleviated in the last decade, producing a great increase in the volume of acupuncture research. The second main reason acupuncture has not been researched more in Western science is the challenge of incorporating Eastern medicine with Western medicine. The Eastern scientific explanations of acupuncture are difficult to understand in Western terms. In traditional Chinese medicine, acupuncture is thought to be effective by correcting balances and flow of energy, known as qi, in the body. Qi flows through 12 meridians, six ying meridians and six yang meridians, each

specifically named for its own organ or function. Acupoints lie on these qi meridians, so, when qi is blocked by physical, mental, or emotional illness, the desired flow of qi may restored by inserting needles in acupoints [1]. The concept of qi is tied to early Chinese philosophy, and though parallel concepts exist in many other cultures, there is no parallel concept in Western science. Furthermore, this foreignness leads to a bias of Western researchers and public. A Wall Street Journal article in 2002 claims that, “until recently, acupuncture was widely regarded as quackery in the U.S.” [8]. In another news article in 2010, an author calls qi “invisible” and “fanciful” [2]. Ironically, an acceptance and upholding of traditional explanations such as qi by many practitioners of acupuncture in the West may further the dismissal of acupuncture by some as an unscientific Eastern practice. Thus, acupuncture remains stigmatized in Western research. Although the mechanism of acupuncture has not yet been captured, the practice of acupuncture can still be carried out with conviction in cases where there is supporting scientific evidence. Unfortunately, this is not reflected in the amount of acupuncture practiced in Western medicine: compared to an estimated 660,000 practicing physicians in the United States (according to the U.S. Census Bureau 2010 statistical abstract) today, there are about 18,000 acupuncturists practicing in the United States, of whom just 3,000 are physicians, although the rest have also completed at least masters-level coursework in acupuncture and passed a standard licensing exam [8]. In some ways, the practice of acupuncture is limited by the amount and quality of research: because scientists do not yet know how acupuncture works, they are not able to freely move from theory to practice by scientifically explaining in what cases acupuncture should be applied. Instead, effects of acupuncture must be determined for specific conditions, so that, for example, verifying benefits from acupuncture to relieve depression during pregnancy cannot be generalized to say that acupuncture may relieve all forms of depression. Despite the difficulties in acupuncture research, the potential benefits merit its pursuit. Acupuncture is a treatment with much evidence for success, small cost, and few to no side effects. It has been practiced extensively and works with the body’s natural healing mechanisms to promote its effects. It is no longer a mystery why acupuncture research ought to become an important investigation in Western science: this part of the case is closed. Talia Retter is in her fourth year at the University Chicago, majoring in Psychology and Biology with a Specialization in Neuroscience.

References 1. Field, Tiffany. (2009). Complementary and alternative therapies research (pp. 43-53). Washington, D.C.: American Psychological Association, vii, 235. 2. Beck, Melinda. (2010, March 24). Trying to decode an ancient therapy --- Hightech tools show how acupuncture works in treating arthritis, back pain and relieving other ills. Wall Street Journal, 27. 3. White, Peter. (2006). A background to acupuncture and its use in chronic painful musculoskeletal conditions. Perspectives in Public Health, 126(5), 219-227. 4. Alderman, Lesley. (2010, May 8). A Chinese art, in the context of the west. New York Times.

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5. Acupuncture. NIH Consensus Statement Online (1997, November 3-5). 15(5):1-34. 6. Lui, S., Smith, E. J., & Terplan, M. (2010). Heterogeneity in search strategies among Cochrane acupuncture reviews: is there room for improvement? Acupuncture in Medicine, 28(3), 149-153. 7. Parker-Pope, Tara. (2010, August 24). Studying acupuncture, one needle prick at a time. New York Times, p. D5. 8. Aches & Claims: Acupuncture: From Quackery to Mainstream. (2002, July 23). Wall Street Journal, p. D3. 9. http://nccam.nih.gov/sites/nccam.nih.gov/files/acupuncture1068hi.jpg

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UCHICAGO

The Criminal Mind Margaret Sivit

oon after his 40th birthday, the schoolteacher from Virginia began to realize he was no longer quite himself. The once-devoted husband had begun making advances toward his female students, while spending his evenings at home pouring over child pornography. His sexual appetite seemed to have turned overnight; as it became increasingly pronounced, he found himself soliciting sex from massage therapists and even seeking out prostitutes. Baffled by his own compulsions, the teacher tried to keep this new, sinister side of himself hidden from his wife and colleagues. However, after he was discovered making advances towards his own stepdaughter, he was removed from his home and received a court order to complete a Sexaholics Anonymous course – which he promptly failed, after soliciting sex from virtually all of the female members and staff [1]. Under any other circumstances, the Virginia schoolteacher would have gone to prison – if, the night before he was scheduled to receive his sentencing, he hadn’t finally gone to see a doctor about the migraines he had been experiencing. It was apparent to University of Virginia neurologists Dr. Russell Swerdlow and Dr. Jeffrey Burns that there was something wrong with their patient, who was having trouble keeping his balance and confessed that he thought he might rape his landlady that evening. Swerdlow and Burns decided to give the teacher an MRI scan – which revealed an egg-sized brain tumor pressing against his right frontal lobe, an area thought to govern self-control and decision-making. When the tumor was removed, the pedophilia vanished with it [2]. “The most interesting part of this,” remarks Swerdlow, “is getting into the hardwiring of morality and free will. It raises the question, how free is free will?” Historically, there have been legal exceptions to the notion that all men have free will; exceptions are made for young children, those acting under extreme emotional duress, and particularly for individuals considered insane: those who have lost the ability to distinguish between right and wrong. In this case, however, the schoolteacher knew what he was doing was wrong, but reported that the “pleasure principle overrode” his rational self [3]. That changes in brain structure can bring about behavioral

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changes has been known since the mid 1800’s when railroad worker Phineas Gage survived an injury that destroyed most of his left frontal lobe. An accidental explosion caused an iron rod to be driven completely through his head, resulting in dramatic changes in Gage’s personality and behavior. The previously “shrewd, smart businessman” became aggressive, profane, and childish. According to Dr. John Martyn Harlow, the doctor who treated Gage after his injury, his patient had lost the ability to distinguish between his “intellectual faculties and animal propensities” [4]. He was so altered from his former state that his friends reported he was “no longer Gage” [5]. For members of the jury, this question of whether the defendant was “himself” at the instance of the crime can be the deciding factor in determining guilt or innocence. The insanity defense is rooted in the belief that rational judgment is the most universal human property, without which the person’s “true” self is somehow not even present in their own body – and therefore cannot be held accountable. In cases like that of the Virginia schoolteacher, it becomes clear that even if the defendant retains the ability to make moral judgments, the urge might be so irresistible that he cannot be said to be in control. This causes juries to ask questions Reproduced from [13] such as, “Was it him or was it his circumstances?” and “Was it him or was it his brain?” [6] If the defendant has brain damage or a tumor, the answer seems simple: it was not him, it was his brain. Using magnetic resonance imaging (MRI) and computed tomography (CT) scans, anomalies in brain structure are fairly easy to identify – and, if the anomaly is a tumor, they are also fairly easy to fix. In the case of Charles Whitman, this type of neuroimaging could have saved his life – as well as the lives of over a dozen others. In 1966, the 25-year-old student made his way to the top floor of the University of Texas tower, hauling with him a footlocker of guns and ammunition. That morning, Whitman had unceremoniously murdered his mother and stabbed his wife to death; once he reached the top of the tower, he began killing with the same emotionless precision. He shot a secretary and several families at point-blank range, then began firing haphazardly at the deck below. In the end,

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UCHICAGO Whitman also killed himself – leaving the police to arrive at a mediate all “executive functions.” In many criminal cases asscene of inexplicable bloodshed. The suicide note discovered sociated with abnormal brain functioning and FLD, the specific later included a request that an autopsy be performed of his region in question is the orbitofrontal cortex, responsible for brain, because Whitman himself suspected that something controlling empathetic and “socially appropriate” behavior fundamental about his thinking had changed. If brain scanning [2]. Frontal Lobe Disorder is marked by “emotional blunting” technologies had been available at the time, Whitman might of the patient, with symptoms including apathy, impulsivity, have lived to discover that he was right: the autopsy revealed and the “inability to empathize with the feelings of others” [2]. a nickel-sized tumor compressing his amygdala, the brain Therefore, behaviors resulting from FLD can be comparable to region associated with controlling fear and violent behavior [3]. that of individuals with frontal or temporal lobe tumors, such However, if Whitman had lived to find out that his violent as Whitman or the Virginia schoolteacher. In the 1999 case of behavior was caused by a tumor, should he still have been Cooper v. State, the court ruled that due to the defendant’s punished? It seems wildly unjust to punish someone for hav- FLD, he “had no judgment, in that he could appreciate the ing cancer, or any other affliction that is entirely outside of criminality of his conduct, but could not conform his conduct their control; on the other hand, Whitman’s actions cannot be to the requirements of the law” [1]. The “irresistible impulse” rightly called involuntary manslaughter, as he was certainly criteria is what separates the FLD defense from the insanity intending to commit murder. As we continue to learn more defense, which requires that the defendant cannot distinguish about the correlation between brain structure and human between right and wrong, much less conform to them. In behavior, it will become increasingly necessary to provide a South Carolina v. Stanko, medical examiners testified that the criterion beyond mere intent – to delineate between the free defendant had an abnormality in his frontal lobe that “imand the unfree will, the self and the non-self, the dividing line paired his ability to control his impulses and exercise proper of legal responsibility. judgment” [7]. Had the defense used this evidence to show The ethics of legal retribution become even more difficult that Stanko suffered from FLD – instead of trying to argue when the cause-and-effect relationship between biology and that he was insane – the 17-year-old might have received a behavior is less clear. Anomalies in brain function cannot al- less severe sentence. ways be identified using relatively unambiguous MRI scans, One problem with creating a legal standard for the FLD which generally require little interpretation. Technologies such defense is that Frontal Lobe Disorder is generally identified as as positron emission tomography (PET) and functional MRI a set of symptoms – it is a functional rather than a structural (fMRI) scanning are significantly less straightforward, because abnormality, with no definitive physical markers. Besides they are an indirect measure of brain activity. Instead, PET fMRI and PET scans, one method used to diagnose FLD is and fMRI scans measure metathe Iowa Gambling Task, which bolic activity in the brain – rate tests a subject’s ability to resist The most interesting part of blood flow and blood-oxygen the urge for instant gratification levels, respectively – which are in favor of a delayed reward [2]. of this is getting into the assumed to be directly associated However, the exact diagnosis of hardwiring of morality and free with neural activity. Accordingly, Frontal Lobe Disorder remains the use of these brain imaging highly contested – according to will. It raises the question, how technologies as evidence in legal Richard Bonnie, professor at the free is free will? cases has yielded mixed results. University of Virginia School of In the 2007 case South Carolina Law, “there is, in short, no ob- Russel Swerdlow v. Stanko, PET scans were used jective basis for distinguishing on behalf of Stephen Stanko, a between... the impulse that was 17-year-old who killed two people and raped a teenage girl. irresistible and the impulse not resisted” [1]. Even so, while PET During the trial, Stanko claimed to be insane, and neuroimages and fMRI technologies are arguably unfit to provide decisive were used to show that Stanko had a brain injury from birth evidence of FLD in legal cases, they are extremely informative that affected his reasoning capabilities. One expert testified that as we begin to understand which brain regions are responsible this brain abnormality prevented Stanko from distinguishing for particular functions – especially when examining such a between right and wrong – the requirement for the insanity vast region as the frontal lobe. defense under South Carolina law. In response, the prosecution Another challenging piece of evidence is the presence presented several witnesses who testified that Stanko could, of certain genes that affect brain chemistry and have recently in fact, make moral distinctions – and therefore could also be been correlated with criminal behavior. Most common among held accountable for his actions [7]. Consequently, the jury them is a variant of the MAO-A gene, which is thought to rejected the insanity defense and sentenced Stanko to death [7]. predispose an individual towards violent, reactive behavior, This case highlights the distinction between insanity and and accordingly has been nicknamed the “warrior gene.” In Frontal Lobe Disorder (FLD), a distinction that legal courts are 2006, a man named Bradley Waldroup, who had this parjust beginning to recognize. Comprised of three overlapping ticular variant of the MAO-A gene, was partially absolved regions – the cingulate gyrus, the dorsolateral region, and the of murder and attempted murder. After his estranged wife orbital frontal lobe – the frontal lobe is generally considered to arrived home with her friend Leslie Bradshaw, Waldroup and

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UCHICAGO his wife got into a raging argument. Waldroup responded by sibility. This creates a dilemma that appears to compromise shooting Bradshaw eight times, splitting her head open with the most essential premise of legal theory itself: namely, that a machete, then chasing his wife with the machete and slicing all rational men are capable of exercising morality, and are her repeatedly. Waldroup originally faced the death-penalty, endowed with free will to actualize their moral decisions. If the but after genetic evidence was brought forward suggesting the sort of determinism suggested by Morse is correct, it implies MAO-A gene had affected his brain chemistry, causing him to that you and I are no more “in control” of our decision-making react violently, Waldroup received only 32 years in prison [8]. than a serial killer with frontal lobe disorder, or a pedophile It is important to note that isolated factors such as genes, with a brain tumor. abnormal activity in a certain brain regions, or even tumors On this note, psychologist Walter Mischel attempts to may not be enough in themselves to “cause” deviant behavior. provide some reassuring evidence. In 1972, Mischel conducted Neuroscientist Jim Fallon, who has done extensive research on a study at Stanford University on the ability of young children the relationship between brain function and behavior at UC- to delay gratification. Each child in the study was given a Irvine [9], has come up with three main criteria for predicting marshmallow – and promised another if he or she could wait whether a particular individual will be involved in criminal twenty minutes without eating the first [12]. Among the fiveactivity, particularly violent crime: the first is that activity in the hundred tormented children in the study, there was a wide orbital frontal cortex, the region range in their abilities to resist the associated with moral decisionurge to eat the first marshmallow. making and ethical behavior, is Ten years later, Mischel conducted More fundamentally, there significantly less active than in a follow-up study; he found that is the question of whether a “healthy” brain; the second is there was an unmistakable corthe presence of the MAO-A gene, relation between self-control in crimes that can be attributed to which regulates serotonin levels childhood and success later abnormal brain activity become early and subsequently affects mood, in life. Notably, those who had sometimes leading to impulsive had the most difficulty resisting morally excusable reactions under stress; the last urges as young children were factor is experiences, particularly more likely to be aggressive and upbringing and if the individual was abused as a child [10]. prone to violent behavior, to have been fired from jobs, and It is the interplay of these factors, Fallon believes, that result even to be overweight as adults. This pattern led many to in a mere predisposition towards crime becoming a reality. conclude that self-control was biologically hard-wired; it was More fundamentally, there is the question of whether proof that the “free” will, as Morse theorized, is not really free crimes that can be attributed to abnormal brain activity become at all. However, Walter Mischel also found that even children morally excusable. It seems natural to distinguish the “self” with the least amount of self-control could be taught – using from physiology when discussing culpability, leading to ques- simple tricks and mental distractions – to vastly improve their tions such as “Was it him or was it his brain?” or even “Was ability to resist impulses. Regardless of whether this is indicait him or was it his genes?” [6]. Ultimately, these may not be tive of an independent “mind” learning to better control the the right questions to be asking. According to Stephen Morse, free will, or merely the conditioning of the causally-effective professor of Law Psychology at the University of Pennsylvania, brain, it could provide the foundation for a justice system the belief that “causation, especially abnormal causation, is based on rehabilitative – rather than retributive – court rulings per se an excusing condition” is the “fundamental psycholegal for those with FLD and other neurological disorders. While error” [6]. All behavior, whether criminal or “healthy,” may be biology may make it more difficult to exercise self-control, said to be the combined sum of multiple genetic, epigenetic, no one, Mischel believes, is incapable of improvement [12]. environmental and neural factors [11]; “there is no ‘him’ independent of these other things” [6]. Therefore, it seems that Margaret Sivit is currently a sophomore at the University of Chicago no matter our perceived deficiencies or abnormalities, we are pursuing a B.A. in English and Philosophy. either all completely responsible, or all absolved of responReferences 1. Redding RE. The Brain-Disordered Defendant: Neuroscience and Legal Insanity in the Twenty-First Century. Am Univ Law Rev. 2006 Oct; 56, (1): 51-127. 2. Seiden JA. The Criminal Brain: Frontal Lobe Dysfunction Evidence in Capital Proceedings. Cap. Def.J. 2004; 16 (2): 395-420 3. Eagleman D. The Brain on Trial. The Atlantic Magazine 2004 July-Aug [cited 2011 Nov]. Available from: http://www.theatlantic.com/magazine/archive/2011/07/thebrain-on-trial/8520/1/ 4. Tworney S. Phineas Gage: Neuroscience’s Most Famous Patient. The Smithsonian Magazine. 2011 Jan [cited 2011 Nov]. Available from: http://www.smithsonianmag. com/history-archaeology/Phineas-Gage-Neurosciences-Most-Famous-Patient. html?c=y&page=1 5. Damasio AR. A Neural Basis for Sociopathy. Arch Gen Psych. 2000; 57: 128-129 6. Greene J, Cohen J. For the law, neuroscience changes nothing and everything. Phil Trans of the Royal Soc. 2004 November 24; (359)1775-1785

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7. South Carolina Judicial Department. State v. Stanko. 2008 February. Available from: www.sccourts.org 8. Hagerty BB. Can Your Genes Make You Murder? National Public Radio. 2010 July. Available from: http://www.npr.org/templates/story/story.php?storyId=128043329 9. University of California – Irvine, Faculty Profile System. Available from: http:// www.faculty.uci.edu/profile.cfm?faculty_id=2303 10. National Public Radio. “Can Genes and Brain Abnormalities Create Killers?” 2010 July. Available from: http://www.npr.org/templates/story/story. php?storyId=128339306 11. Human Genome Project: Information. Available through: www.genomincs. energy.gov 12. Abumrad J, Krulwich R. Fate and Fortune. Radiolab. 2010 Oct; 8 (5). Available from: http://www.radiolab.org/2010/oct/15/ 13. http://www.nlm.nih.gov/visibleproofs/media/detailed/vi_c_364.jpg

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BROWN

The Bright Side of the Black Market: The Case of Street Suboxone Sandeep Manel Nayak

t’s a miracle drug,” says Casey, a Providence heroin addict. Approved for opiate detoxification and short- and long-term maintenance in 2002, suboxone is the latest and greatest development in the medical establishment’s continual push to treat addiction as a disease rather than moral failure or sin. The first such maintenance drug, methadone, made its appearance in a storm of controversy. However, efforts to overcome these public relations tribulations eventually made methadone maintenance therapy an accepted practice, by legitimizing the principles of opioid maintenance and harm reduction. Methadone acceptance in turn has paved a relatively controversy-free way for suboxone’s debut. Yet still, access to this valuable medicine remains inadequate. While, in crude terms, methadone might be thought of as long-lasting heroin, the common accusation that maintenance therapy trades one addiction for another is misleading. Withdrawal is an unpleasant experience, and those in its grip will go to great, even destructive lengths to avoid it. Plain and simple, it’s addiction. Thus methadone (and opioid maintenance more generally) alleviates the physical agony and destructive social behaviors of addiction without curing it. While many people wean themselves off to an opiate-free lifestyle, others may remain in maintenance for life. Regardless, methadone maintenance works; it has consistently proven better than “going cold turkey” at reducing heroin use and overdose deaths. Yet despite its efficacy, perceptions of methadone maintenance among opioid abusers are generally negative [1,2]. Casey’s attitude towards the treatment, by no means unique, can be summed up in the succinct: “Fuck that shit” [12]. Withdrawal from methadone can be agonizing, dragging on for weeks, and its abuse potential has resulted in stringent regulations on its use, normally requiring that patients show up daily to a special clinic for their dose. A hassle indeed. Enter Suboxone Unlike methadone, heroin, and every other abused opiate mentioned in the news, suboxone is only a partial (as opposed to full) opiate agonist. Moreover, suboxone has a higher binding affinity to opiate receptors than most abused opiates. Taken together, this means that if an addict, with, say, heroin plugging

his opiate receptors were to slide a suboxone tablet under his tongue, it would actually precipitate withdrawal by replacing the heroin with a less effective receptor stimulant. This also means that if another opiate were taken on top of a suboxone dose, its effects would for the most part be blocked. All of this makes it even harder to abuse by people who are already addicted [3]. As a consequence of not being a full agonist, there is a “ceiling effect” of suboxone dosing, so that after a certain amount (about 32 mg) higher drug concentrations produce little to no additional effect [4]. Thus, severely dependent individuals needing a greater dose will get little benefit from suboxone. However, this ceiling effect also blocks overdose (as long as the medicine is not mixed with other drugs). Furthermore, suboxone withdrawal is regarded to be milder than methadone and heroin by both injection drug users as well as the medical establishment [2,3]. Even sudden suboxone cessation does not generally lead to severe symptoms, a fact which is recognized and appreciated by surveyed opioid abusers. Withdrawal from methadone, however, is perceived to be (and is) more severe and more prolonged than heroin withdrawal [2,5]. Moreover, suboxone is really a combination of two drugs: one, the active ingredient, buprenorphine, and the other, an inactive opioid blocker which only takes effect when injected. If a misinformed drug user tries to inject suboxone for recreational purposes, he will at best waste his money since the blocker will prevent the buprenorphine from producing any euphoric effect. However, if he had taken some other opiate prior, the blocker will kick those out of the receptors, too, thereby precipitating an irritating withdrawal. This quality essentially rules out the possibility of suboxone’s abuse by injection [3]. Thus, chemically, suboxone is shockingly well-equipped for reducing abuse potential. On top of this, it works about as well as methadone (6). In contrast to early-morning methadone clinic visits and long waits in lines to get dosed, suboxone patients need only make occasional (and private) trips to a doctor’s office to renew their prescription. Given all this, it is no surprise that opioid abusers generally regard suboxone in a more positive light than methadone [1,2,7].

Reproduced From [13]

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BROWN Access of diverted prescription opiates, including oxycodone and Suboxone’s availability, however, is still restricted. For example, hydrocodone which are obviously used in ways that might be doctors wishing to prescribe suboxone have to go through termed abusive. That is to say, people purchasing such drugs an eight-hour training course to do so, and are limited to are generally not following standard medical procedure in treating one hundred patients at a time. While this might seem their uses of them. reasonable, no such restrictions are levied on the prescription What’s interesting about diverted suboxone is that it is of more easily abused opiates, such as Vicodin. Moreover, by and large being used in a medically-appropriate way. In injection drug users (IDUs) form a generally disenfranchised Providence, eighty-six percent of IDU respondents reported ever population that doesn’t often have health insurance or large obtaining street suboxone, and among these, eighty-four percent sums of disposable cash . In the Providence study, the majority reported having used it to reduce withdrawal symptoms, versus of those surveyed had no health insurance, and the ones that only thiry-two percent to get high. Moreover, seventy-seven did typically had some sort of state-funded healthcare such percent of those who’d used diverted suboxone in Providence as Medicaid, which most suboxone providers in Rhode Island cited doing so because they couldn’t afford treatment [8]. don’t accept [8]. Studies from Sweden, Baltimore and elsewhere also evidence Thus, many IDUs wishing to acquire suboxone through the low rate of abuse of illegally-obtained suboxone [10,11]. legal channels have to pay “out of pocket.” One Providence A survey of Providence injection drug users found that doctor blogged: “I like to charge $350 for the initial evaluation, while more respondents were interested in enrolling in suboxone $200 for the induction [into treatment], and $150 for followup treatment than methadone, three times as many had registered [sic] appointments. Cash only.” [9]. in methadone programs in the past year [8]. This demand for This, however, doesn’t even include the cost of the suboxone suboxone is being filled by diverted drugs. In Providence, for itself, which in this particular case “alone averages around $150 example, more than twice as many survey respondents had per month for most people.” So illegally obtained suboxone in a month’s supply of thirty 8 mg the past month than had received In Providence… more tablets would amount to five it legally in the past year [8]. dollars each, not including the Casey detoxed herself with than twice as many survey costs of doctor visits, lab work, diverted suboxone on three respondents had illegally etc. It is, as the aforementioned occasions. While she relapsed doctor says, “expensive” [9]. each time, suboxone gave obtained suboxone in the past Interestingly, on the street, her a respite, no matter how month than had received it the price for the pills themselves brief, from an addiction that is about the same. A Baltimore seemed otherwise unbreakable. legally in the past year study reported a cost of five Clearly, unsupervised use of dollars per 8 mg tablet, and the any medicine is not ideal, and previous Providence one reported a median price of six dollars perhaps under the umbrella of proper medical care, she might each [8, 10]. By removing doctors’ fees, it is actually cheaper have been able to enter a more lasting period of abstinence. to acquire suboxone through illegal channels. While Casey However, given today’s barriers to suboxone access and the would have liked to receive authorized suboxone treatment drug’s exceptional safety profile, it’s difficult to criticize this in the form of a doctor’s prescription, her lack of insurance kind of illegal therapeutic use, particularly when considering compelled her to the economically rational choice of purchasing the alternative ways of dealing with withdrawal. For the time street suboxone. being then, might suboxone diversion be a good thing? The Uses and Abuses of Street Suboxone Prescription drug diversion is hardly a new phenomenon. The streets of American cities play host to a thriving black market

Sandeep Nayak is a senior Religious Studies concentrator with interests in public health, political science, sociology, and how real world topics span a variety of academic disciplines.

References 1. Schwartz RP, Kelly SM, O’Grady KE, Mitchell SG, Peterson JA, Reisinger HS, et al. Attitudes toward buprenorphine and methadone among opioid-dependent individuals. Am J Addict. 2008 Sep-Oct;17(5):396-401. 2. Zaller ND, Bazazi AR, Velazquez L, Rich JD. Attitudes toward methadone among out-of-treatment minority injection drug users: implications for health disparities. Int J Environ Res Public Health. 2009 Feb;6(2):787-97. 3. Jones HE. Practical considerations for the clinical use of buprenorphine. Sci Pract Perspect. 2004 Aug;2(2):4-20. 4. Walsh SL, Preston KL, Stitzer ML, Cone EJ, Bigelow GE. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther. 1994 May;55(5):569-80. 5. Gossop M, Strang J. A comparison of the withdrawal responses of heroin and methadone addicts during detoxification. Br J Psychiatry. 1991 May;158:697-9. 6. Johnson RE, Chutuape MA, Strain EC, Walsh SL, Stitzer ML, Bigelow GE. A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N Engl J Med. 2000 Nov 2;343(18):1290-7.

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7. Stancliff S, Myers JE, Steiner S, Drucker E. Beliefs about methadone in an inner-city methadone clinic. J Urban Health. 2002 Dec;79(4):571-8. 8. Bazazi AR, Yokell M, Fu JJ, Rich JD, Zaller ND. Illicit use of buprenorphine/ naloxone among injecting and noninjecting opioid users. J Addict Med. 2011 Sep;5(3):175-80. 9. Rich JD. Suboxone Cost: For Medication and Treatment? [cited 2011 October 16]; Available from: http://www.allaboutsuboxone.com/suboxone-cost-for-medicationand-treatment/. 10. Gwin Mitchell S, Kelly SM, Brown BS, Schacht Reisinger H, Peterson JA, Ruhf A, et al. Uses of diverted methadone and buprenorphine by opioid-addicted individuals in Baltimore, Maryland. Am J Addict. 2009 Sep-Oct;18(5):346-55. 11. Hakansson A, Medvedeo A, Andersson M, Berglund M. Buprenorphine misuse among heroin and amphetamine users in Malmo, Sweden: purpose of misuse and route of administration. Eur Addict Res. 2007;13(4):207-15. 12. Casey. Interviewed by: Nayak S. Feb 2011. 13. http://gdna.georgia.gov/02/gdna/home/0,2803,132319894,00.html

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CORNELL

Reading Reinvented: How Computers and the Internet are Influencing our Society Latha Panchap

In the mind of the average computer user, the internet to describe “a deep but effortless involvement that removes has the answers to almost all of life’s questions. Be- from awareness the worries and frustrations of everyday life.” tween the search engines and the millions of constantly Paper novel enthusiasts can identify with this familiar feeling: updated webpages, the internet gives users the becoming immersed in a novel and losing all Reproduced from [13] ability to know everything that has happened, sense of time. This state of full absorption in is happening, and might happen, all at their reading is difficult to achieve with a computer. fingertips. This is the internet’s greatest gift: Instant messages, emails, music, and pop-up unlimited information. However, recent discovads distract us and cause frequent breaks in eries about the internet’s effect on Americans’ our ‘flow’. [4] reading skills show that such technology may Attention blindness is a crucial part have significant repercussions on society and of achieving ‘flow’. Cognitively, this can be today’s youth. explained through the actions of neurons. NeuA 2010 study from the Pew Research rons fire off in pathways to complete certain Center shows that Americans spend an average actions, such as reading. As these pathways are of 60 hours a month on the Internet. American repeated more often, the neurons link together, internet users spend 42% of this time viewing and the actions are performed more efficiently. internet content, such as blogs and articles. [1] The growing Eventually, these actions become automatic reflexes that pass concern among parents and teachers, however, is that this undetected under our radar of attention. This is known as time spent surfing Fanfiction.net or Tumblr could be used attention blindness. Reading is an automatic reflex, meanto do something more intellectually stimulating. [2] A study ing that our neurons are already wired together in efficient released in 2004 by the National Endowment of the Arts (NEA) pathways to do this task. Because of this, we are subject to indicates that the decrease in the number of novels read by attention blindness while reading. Professor Cathy Davidson teenagers may be a crucial reason for the drop in standard- feels that people pay attention to actions, responses, and ideas ized reading test scores. [3] Chairman of the NEA, Dan Gioia, for which their neurons have not formed pathways. Therefore, believes that the Internet and its many distractions may be when pop-ups or instant messages appear on the screen, we one of the main sources of this automatically pay more attention decline, signified by his statement to these distractions than to the “[The benefits of newer electronic text. [6] Instant messages, emails, media] provide no measurable The internet’s negative efsubstitute for the intellectual and fects go much deeper than dismusic, and pop-up ads distract personal development initiated tracting and taxing the user. In us and cause frequent breaks in and sustained by frequent readhis article “Is Google Making Us ing.” [2] Stupid?” Nicholas Carr voices our ‘flow’ Gioia’s claim brings up the worry that many readers an interesting point: What exactly now have— that the internet is is the difference between readinfluencing the way we process ing in print and reading online? In their book The Myth of information. According to Carr, we no longer possess the focus the Paperless Office, cognitive psychologist Dr. Abigail Sellen and thought to deeply understand what we are reading, only and researcher Richard Harper come to the conclusion that the ability to skim and superficially grasp the meaning of the navigating a webpage requires more brain power than turn- text. [7] Dr. Jakob Nielsen, who holds a degree in humaning the pages of a novel. Furthermore, the light-producing computer interactions, claims that humans’ method of reading screens of computers force our eyes to constantly focus and has actually changed— our new reading pattern consists of web refocus. [4] This difficulty alone causes users to read 25% searches and scanning, paying attention to small paragraphs, slower on screen than on paper. [5] In addition, the many bolded words, headings, and lists. [8] His eyetracking study, distractions of the internet cause readers to lose ‘flow’, a term which observed the eye movements of 232 users, showed that used by psychology professor Dr. Mihaly Csikszentmihalyi people scan websites using a rough F-pattern, reading the first

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CORNELL two paragraphs and then scanning the left side of the page. learn from what others have posted. Although this content [9] Nielson’s conclusion is that computer users have become may not always come from a reliable source, studies show that ‘information foragers’. Like jungle animals scavenging for food, the collaboration of many individuals on one subject’s Wiki we’ve learned to scan websites for page can lead to very accurate information, find what we need, content. Wikipedia, for example, and move on to the next website. was found to have an error rate Google’s desire to create [10] Search engines like Google close to that of Encyclopedia and Bing have encouraged this Britannica, a highly-regarded “the perfect search engine” process by organizing pertinent scholarly encyclopedia. Howconsequently takes all the work webpages into one list and giving ever, Wikipedia differs from snippets of text to summarize the Encyclopedia Britannica in that if out of actively searching for contents of each site. Google’s found, these errors can be fixed information and discourages desire to create “the perfect search immediately by anybody with engine” consequently takes all internet access. [12] Senchyne people from exhausting a the work out of actively searching believes that this type of instant single source before finding for information and discourages sharing and editing has allowed people from exhausting a single computer users, especially stuanother source before finding another.[7] dents and younger children, to Proponents of this internet become “social readers” who now revolution argue that the benefits read the article, then discuss it of the internet far outweigh the aforementioned repercus- in forums with one another. sions. Experts in early childhood development claim that the Access to unlimited information and multiple perspectives interactive interface of the internet promotes the development makes the internet an invaluable source for young Americans of literacy and problem-solving skills, as well as the ability to in the process of developing synthesis and problem-solving synthesize information from multiple sources. [11] Educators skills. However, the internet’s many distractions and its comsupporting the use of the web as a reading medium believe that plicated interface can cause us to lose focus on what we are it can also provide many different perspectives and a wider, reading. Over the years, our brains have learned to overcome more comprehensive view of a subject. Computer-based read- these challenges by skimming articles for answers instead of ing’s strong influence on American children caused literacy gaining a deep understanding of the text. As the influence of experts to advocate the addition of a computer component the internet continues to grow, the differences between reading to the Nation’s Report Card, an annual study conducted to paper text and reading online will become more pronounced, measure the proficiency of the nation’s youth in a variety of as will the effects of web-based reading on the way we read, subject areas. [2] write, think, and communicate. During this revolution, we Mr. Jonathan Senchyne, a doctoral candidate in English at must stay aware of these differences and either learn to adapt Cornell University, believes that the ability to instantly share our daily lives to this new system of thinking or find a way and edit information is another huge advantage of internet to control the degree to which the internet influences our reading (J. Senchyne, personal communication, October 27, daily lives. 2011). The invention of blogs and other types of self-publish sites has granted everyone the ability to express their opinion to Latha Panchap is currently a freshman at Cornell University majoring the world at large. Wikis, for example, have become a popular in Biological Engineering and minoring in Business. way for people to share the information that they have and References 1. Smith C. Internet Usage Statistics: How We Spend Our Time Online (INFOGRAPHIC). Huffington Post [Internet]. [homepage on the Internet]. 2010 Jun 22 [cited 2011 Oct 3]; Tech: [about 2 screens]. Available from: http://http://www. huffingtonpost.com/2010/06/22/internet-usage-statistics_n_620946.html 2. Rich M. The Future of Reading - Literacy Debate - Online, R U Really Reading?. The New York Times [Internet]. 2008 Jul 27 [cited 2011 Oct 07]; Arts [about 10 screens]. Available from: http://www.nytimes.com/2008/07/27/books/27reading. html?pagewanted=all 3. Rich M. Study Links Drop in Test Scores to a Decline in Time Spent Reading. The New York Times [Internet]. 2007 Nov 19 [cited 2011 Oct 02]; Arts [about 3 screens]. Available from: http://www.nytimes.com/2007/11/19/arts/19nea.html?adxnnl=1&ref= books&adxnnlx=1326294343-Nkr+Fh/sP757DBsEwL2+sQ 4. Powers W. Hamlet’s Blackberry: Why Paper is Eternal. Joan Shorenstein Center on the Press, Politics and Public Policy Discussion Paper Series. Cambridge: Harvard College; 2007. p. 1-74. 5. Nielsen J. Useit.com: Jakob Nielsen’s Website. [homepage on the Internet]. 1997 [cited 2011 Sep 30]. Why Users Scan Instead of Read; [2 screens] Available from: http://www.useit.com/alertbox/whyscanning.html 6. Davidson C. Now You See It: How the Brain Science of Attention Will Transform the Way We Live, Work, and Learn. New York: Viking; 2011. 7. Carr N. Is Google Making Us Stupid?. The Atlantic [Internet]. 2008 [cited 2011

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Oct 02]; Magazine: [about 8 screens]. Available from: http://www.theatlantic.com/ magazine/archive/2008/07/is-google-making-us-stupid/6868/ 8. Nielsen J. Useit.com: Jakob Nielsen’s Website. [homepage on the Internet]. 1997 [cited 2011 Sep 30]. How Users Read on the Web; [3 screens] Available from: http:// www.useit.com/alertbox/9710a.html 9. Nielsen J. Useit.com: Jakob Nielsen’s Website. [homepage on the Internet]. 2006 [cited 2011 Sep 30]. F-Shaped Pattern For Reading Web Content; [3 screens] Available from: http://www.useit.com/alertbox/reading_pattern.html 10. Nielsen J. Useit.com: Jakob Nielsen’s Website. [homepage on the Internet]. 2003 [cited 2011 Sep 30]. Information Foraging: Why Google Makes People Leave Your Site Faster; [4 screens] Available from: http://www.useit.com/alertbox/20030630.html 11. Johnson G. Internet Use and Cognitive Development: a Theoretical Framework. E-Learning Digital Media. 2006 [cited 2011 Oct 25] 3(4): [8 pages]. Available from: http://www.wwwords.co.uk/pdf/freetoview.asp?j=elea&vol=3&issue=4&year=2006& article=7_Johnson_ELEA_3_4_web 12. Shu W, Chuang Y. The Behavior of Wiki Users. Soc Behav Personal [serial on the Internet]. 2011 [cited 2011 October 25]; 39(6): [14 pages] Available from: http://web. ebscohost.com/ehost/detail?sid=b1debc69-81bf-4fb4-a76a-01113140993%40session mgr110&vid=4&hid=112&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#db=aph& AN=62718753 13. http://tntel.tnsos.org/images/books-mouse.jpg

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CORNELL

The Chemistry of Medicinal Plants: Phytochemicals as Novel Chemotherapeutic & Biomedical Interventions Spenser Reed

physician writes a prescription for 100 mg resveratrol (the antioxidant phenolic compound found in red wine) for your hypercholesterolemia. You go in for a routine check-up and discover the local outpatient clinical dispensing Indian frankincense (Boswellia serrata) for the treatment of joint and musculoskeletal pain. The next time you enter a pharmacy, standardized extracts of phytochemicals from hundreds of botanical species line the shelves. Could this be the future of allopathic medicine? For most of the world’s remaining indigenous populations, this is what conventional medicine looks like. Even in animals, one can observe self-medication by use of many botanical species such as in the wild Uganda chimpanzee diet; among the 163 plants chimpanzees are known to eat, 35 (21.4%) are used in traditional African medicine to treat intestinal parasites, skin infections, decreased fertility and others [1, 9]. The art and science of botanical medicine, referred to as phytomedicine or phytopharmacology, is the study of the medicinal properties of plants chemical constituents (phytochemicals) and their applications in the development of pharmaceuticals [1].

were the main therapeutic agents used by humans. Medical anthropological studies of Neanderthal diets and gravesites in the Paleolithic era provide fascinating research about the etiology of modern-day botanical medicine [2-4]. Such studies found a 60,000-year-old gravesite in modern-day Iraq where a man was buried surrounded by [6] documented medical plants, including species in the families Ephedraceae (eg.,epehdra) and Asteraceae (eg., sunflower). Phytochemicals extracted from these plants, such as the alkaloid ephedrine, show stimulant, bronchodilator, vasodilator, analgesic and antihistamine properties. Moreover, macrofossils [5] of the medicinal and psychoactive plants Nymphaea nouchali, Eucalyptus camaldulensis and Mandragora officinarumin have been found at burial mounds across modern-day Europe [6,7]. Even ancient Iberian civilizations used medicinal plants such as Uncaria tomentosa (Cat’s Claw) and Olea europaea (Olive) as antipyretics, anti-hypertensives and immune tonics [7]. Since the use of these phytochemicals by ancient populations thousands of years ago, modern science built upon their clinical applications in disease pathology. Among the varied health benefits include therapeutic properties as chemoprevention, immunomodulation, protection against reactive oxygen species (ROS) and down-regulation of inflammatory cascades, all of which play a crucial role in cellular and biochemical propagation of chronic disease.

As the authors stated, turmeric represents a “promising chemo-preventive and anticarcinogenic agent”

Figure 1: Common foods studied for their relevant phytochemicals. Adapted from Surh Y. Nature Reviews Cancer. 2003; 3, 768-780. Reproduced from [42]

Plants as Ancient Medicine Understanding intrinsic health properties of plants dates back to ancient civilizations. Until the mid-19th century, plants

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Clinical Applications in Allopathic Medicine: Cancer According to the World Health Organization (WHO), cancer is a leading cause of death worldwide and accounts for around 13% of all mortalities [11]. Consequently, much of the research on clinical phytochemicals focuses on chemoprevention, or the prevention or delay of tumorigenesis (the production of new tumors) via natural agents. Although no ‘magic bullet’ exists for cancer treatment, many epidemiologists believe that an average of 35% of human cancer mortality is attributable solely to diet,

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CORNELL [12] and further research from similar diet-cancer connection studies report that certain phytochemicals possess intrinsic anticarcinogenic and anti-mutagenic properties which are vital to preventing and treating cancer growth. Although the survival rates from cancers are slightly higher in recent years, traditional forms of treatment, mainly chemotherapy and radiation, fail to match the new advances in current biomedical therapies [12a]. Chemotherapy and radiation are wrought with serious and often lethal side-effects, such as infection, infertility and neuropathy. Thus, the dire need for cancer therapies free of these side-effects allows phytochemical research to step forward as a possible alternative [12b]. Well-known phytochemicals that show clinical applications in cancer include curcumin,

epigallocatechingallate (EGCg), sulforaphane glucosinolate, and resveratrol. These phytochemicals show much promise in disease treatment because they are efficacious, relatively free from side-effects and have very few contraindications even when used alongside pharmacological cancer interventions. Curcumin, a yellowish pigment extracted from the spice turmeric (Curcuma longa), displays a potent ability to trigger apoptosis, [13] or programmed death of harmful cells. Its chemical action against cancerous growths can inhibit stomach, [14, 15] liver, [16] colorectal, and breast tumors in many models [17, 18]. Placebo-controlled studies have shown its clinical benefits comparable to many nonsteroidal anti-inflammatory drugs (NSAIDs), exemplifying its use in down-regulating in-

Figure 2: Proposed mechanism of action for phytochemical retardation of carcinogenesis. Adapted from Surh Y. Nature Reviews Cancer. 2003; 3, 768-780. Reproduced from [43]

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CORNELL flammatory pathways [19-21]. Fascinating epidemiological evidence has begun to expound on tumeric’s health benefits in the Indian population. According to the World Health Organization (WHO), cancer rates are considerably lower in India compared to similar developed countries such as the United States, France or England [22]. This herb, responsible for the reddish-orange color in Indian curry spice, led epidemiological researchers at the National Institutes of Health’s National Cancer Institute (NCI) to conclude that the decreased rate of the seven common types of cancers ascertained in their study was in large part due to the biochemical effects of turmeric. As the authors stated, turmeric represents a “promising chemopreventive and anti-carcinogenic agent” [23]. EGCg, a flavonoid antioxidant from tea leaves, shows anti-carcinogenesis in a variety of animal models of cancer including cancer of the skin, lung, mouth, esophagus, stomach, colon, pancreas, bladder and prostate [24-26]. Sulforaphane glucosinolate, an antioxidant extracted from cruciferous vegetables (brussels sprouts, broccoli, et al.), also exhibits potent suppression of tumor growth in mammary, colon, and pancreatic cancers [27, 28]. It even has the ability to upregulate hepatic phase I and II detoxification pathways, carrying promise for alcoholic cirrhosis and drug-related hepatotoxicity [29]. Additionally, it has received approval for numerous current NIH Phase I and II clinical trials assessing its potential in treating prostate

Book 1.indb 39

cancer [30]. Resveratrol is a polyphenolic compound found in grape skins, red wine, juices and some berries [31]. It originally caught the attention of scientists when epidemiological studies tried to explain the ‘French Paradox’, whereby French nationals have lower incidences of cardiovascular disease and cancer even with an increased rate of smoking and alcohol consumption [32]. Since these earlier studies, clinical trials show resveratrol exhibits potent antioxidant, anti-carcinogenic, anti-inflammatory, and anti-estrogenic effects [33-36]. Likewise as with other phytochemicals, it inhibits tumor formation and angiogenesis (processes vital to the viability of cancer cells) [37]. Scientists believe resveratrol’s actions may help to prevent and treat cardiovascular diseases, cancers and may even extend longevity, by the activation of SIRT1 genetic activity in humans [38-41]. The Future of Phytochemicals According to Manuel Aregullin, Ph.D., a natural products chemist at Cornell University, “the vast majority of plants that actually exist in the biosphere as promising sources for this chemistry have gone unassessed and untapped in their potential for medicinal use.” Our most fundamental of medicines have their genesis in nature; salicylic acid from White Willow as a source of aspirin and lovastatin from certain fungal species for hyperlipidemia are a Figure 3: Resveratrol is found in few examples. Have we highest concentrations in red grapes exhausted the therapeutic and wine. Reproduced from [44], [45] nature of most plant species? Are we looking hard enough? Undoubtedly, one of the major biases to this type of healing is that herbal supplements are generally viewed as inadequate in providing therapeutically relevant doses to deliver health benefits as a pharmaceutical may be able to do. However, as Dr. Aregullin states, “this is not exactly the correct way to assess efficacy. Rather, these types of herbals have their place in treating acute and chronic maladies as adjuvants to more allopathic types of treatments.” The current research in phytochemicals shows a continuum of pharmacological action, from mild remedies as fever reducers to potent inhibitors of cyclooxygenase (COX) enzymes and down-regulators of inflammatory pathways. Altogether, these findings

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CORNELL show the huge variety of plants and their phytochemical applications in health; “…as these plant chemicals continue to go through more rigorous evaluations and their mechanisms of action elucidated, scientists might understand and appreciate their relevance even more,” Dr. AregulReproduced from [46] lin emphasized. Could you have Manuel Aregullin, Ph.D. thought that the curry you spice Natural Products Chemist, Cornell University & your food with, the melons you Weill Cornell Medical College eat for breakfast, or the tea you drink before bedtime could be preventing cancer cells from proliferating in your body? There are so many biologically relevant plant chemicals which hold much promise as a future treatment for our society’s most prevalent and complicated chronic diseases. Study after study, new phytochemicals show impressive properties that may one day exist as the next con-

ventional approach toward treating our most deadly diseases. Ask yourselves, “Could plants be future biomedical therapies in chronic diseases?” As supported by continuing research in this field, Dr. Aregullin states, “the uniqueness of plants, their use and pharmacology provide clues for scientists to elucidate biologically active and relevant chemistry, which may one day exist as treatment for a disease.”

References

22. Fenley J, Bray F, Pisani DMe. World Health Organization. GLOBOCAN 2000: Cancer incidence, mortality and prevalence worldwide. Lyon, France: IARC Press; 2001. 23. Sinha R, Anderson DE, McDonald SS, Greenwald P. Cancer Risk and Diet in India. J Postgrad Med. 2003; 49: 222-228. 24. Lambert JD, et al. Mechanisms of cancer prevention by tea constituents. J Nutr. 2003; 133(10): 3262S-3267S. 25. Yang CS, et al. Inhibition of carcinogenesis by tea. Annu Rev Pharmacol Toxicol. 2002; 42: 25-54. 26. Lin JK. Cancer chemoprevention by tea polyphenols through modulating signal transduction pathways. Arch Pharm Res. 2002; 25: 561–571. 27. Grubbs CJ, et al. Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol. Anticancer Res. 1995; 15(3): 709-716. 28. Talalay P et al. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry. 2001; 56(1): 5-51. 29. McCarty MF. Inhibition of CYP2E1 with natural agents may be a feasible strategy for minimizing the hepatotoxicity of ethanol. Med Hypotheses. 2001; 56(1): 8-11. 30. National Institutes of Health (NIH) Clinical Trial Database. http://clinicaltrials. gov/ct2/results?term=Sulforaphane 31. Burns J, et al. Plant foods and herbal sources of resveratrol. J Agric Food Chem. 2002; 50(11): 3337-3340. 32. St Leger AS, et al. Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine. Lancet. 1979; 1(8124): 1017-1020 33. Frankel EN, et al. Inhibition of human LDL oxidation by resveratrol. Lancet. 1993; 341(8852): 1103-1104. 34. Yang SH, et al. Genome-scale analysis of resveratrol-induced gene expression profile in human ovarian cancer cells using a cDNA microarray. Int J Oncol. 2003; 22(4): 741-750. 35. de la Lastra CA, et al. Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications. MolNutr Food Res. 2005; 49(5): 405-430. 36. Tangkeangsirisin W, et al. Resveratrol in the chemoprevention and chemotherapy of breast cancer. Phytopharmaceuticals in Cancer Chemoprevention. CRC Press. 2005: 449-463. 37. Aggarwal BB, et al. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res. 2004; 24(5A): 2783-2840 38. Lekakis J, et al. Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. Eur J Cardiovasc Prev Rehabil. 2005; 12(6): 596-600. 39. Li ZG, et al. Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by resveratrol. Carcinogenesis. 2002; 23(9): 1531-1536. 40. Tessitore L, et al. Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21(CIP) expression. Carcinogenesis. 2000; 21(8): 1619-1622. 41. Barger JL, et al. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS One. 2008; 3(6): e2264. 42. http://www.resveratrolnews.com/wp-content/uploads/2011/12/phytochemicalshormetic-effect.jpg 43. http://www.nature.com/nrc/journal/v3/n10/images/nrc1189-f1.jpg 44. http://www.abc.state.va.us/stores/images/redwine.jpg 45. http://www.ars.usda.gov/is/kids/plants/story14/redGrapes.gif 46. http://vivo.cornell.edu/file/n1497/_main_image_aregullin_manuel_thumb.gif

1. DeSmet, PA. The role of plant-derived drugs and herbal medicines in healthcare. Drugs. 1997; 54(6): 801-40. 2. Lietava, J. Medicinal plants in a Middle Paleolithic grave Shanidar IV. J Ethnopharmacol. 1992; 35(3): 263-6 3. Henry, AG. Microfossils in calculus demonstrate consumption of plants and cooked foods in Neanderthal diets (Shanidar III, Iraq; Spy I and II, Belgium). Proc Natl Acad Sci U S A. 2011; 108(2): 486-91. 4. Cordain L, et al. Origins and evolution of the Western diet: health implications for the 21st century”. Am J ClinNutr.2005; 81(2): 341–54. 5. Abourashed, EA. Ephedra in perspective--a current review. Phytother Res. 2003; 17(7): 703-12. 6. Merlin, MD. Archaeological evidence for the tradition of psychoactive plant use in the old world. Economic Botany. 2003; 57(3): 295-323. 7. Camejo-Rodrigues, J. An ethnobotanical study of medicinal and aromatic plants in the Natural Park of Serra de São Mamede. J Ethnopharmacol. 2003; 89: 199–209 8. MA Huffman. Animal self-medication and ethnomedicine: exploration and exploitation of the medicinal properties of plants. Proc Nut Soc. 2003; 62: 371-381 9. Krief, S. Ethnomedicinal and bioactive properties of plants ingested by wild chimpanzees in Uganda. J Ethnopharmacol. 2005; 101(1-3):1-15. 10. http://plantbio.cornell.edu/cals/plbio/directory/faculty.cfm?netId=er30 11. World Health Organization (WHO) Cancer Factsheet. GLOBOCAN 2008 (IARC) Section of Cancer Information (24/10/2011). http://www.who.int/mediacentre/ factsheets/fs297/en/index.html 12. Doll, R et al. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J. Natl Cancer Inst.1981; 66, 1191–1308. 12a. National Cancer Institute (NCI). Cancer Treatments: http://www.cancer.gov/ cancertopics/treatment/types-of-treatment 12b. Lamson DW, et al. Antioxidants in cancer therapy; their actions and interactions with oncologic therapies. Altern Med Rev 1999; 4: 303-328. 13. Sharma RA, et al. Curcumin: The story so far. Eur J Cancer. 2005; 41(13): 19551968. 14. Ikezaki S, et al. Chemopreventive effects of curcumin on glandular stomach carcinogenesis induced by N-methyl-N’-nitro-N-nitrosoguanidine and sodium chloride in rats. Anticancer Res. 2001; 21(5): 3407-3411 15. Huang MT, et al. Inhibitory effects of dietary curcumin on forestomach, duodenal, and colon carcinogenesis in mice. Cancer Res. 1994; 54(22): 5841-5847. 16. Chuang SE, et al. Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis. Carcinogenesis. 2000; 21(2): 331-335. 17. Rao CV, et al. Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound. Cancer Res. 1995; 55(2): 259-266. 18. Pereira MA, et al. Effects of the phytochemicals, curcumin and quercetin, upon azoxymethane-induced colon cancer and 7,12-dimethylbenz[a]anthracene-induced mammary cancer in rats. Carcinogenesis. 1996; 17(6): 1305-1311. 19. Deodhar SD, et al. Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Indian J Med Res. 1980; 71: 632-634. 20. Satoskar RR, et al. Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. Int J Clin Pharmacol Ther Toxicol. 1986; 24(12): 651-654. 21. Plummer, S. M. et al. Inhibition of cyclooxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kB activation via the NIK/IKK signaling complex. Oncogene. 1999; 18: 6013–6020.

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Spenser Reed is currently a sophmore at Cornell University majoring in Food and Nutritional Science and minoring in Global Health.

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ACKNOWLEDGMENTS

The Triple Helix at the University of Chicago would like to sincerely thank the following groups and individuals for their generous and continued support: University of Chicago Student Government Annual Allocations Student Government Finance Committee (SGFC) Bill Michel, Assistant Vice President for Student Life and Associate Dean of the College Arthur Lundberg, Assistant Director for the Student Activities Center Ravi Randhava, Student Activities Resource Advisor Dr. Jose Quintans, William Rainey Harper Professor and Master of the Biological Sciences Collegiate Divison, Advisor to The Triple Helix Dr. Harald Uhlig, Professor in Economics and the College and Chairman of the Department of Economics Dr. Lainie Ross, Carolyn and Matthew Bucksbaum Professor, Professor of Pediatrics, Medicine, Surgery and The College, and Associate Director, MacLean Center for Clinical Medical Ethics Dr. Matthew Tirrell, Founding Director of the Institute for Molecular Engineering The Biological Sciences Department The Physical Sciences Department The Social Sciences Department All of our remarkable Faculty Review Board Members

ÂŠ 2012 The Triple Helix, Inc. All rights reserved. The Triple Helix at the University of Chicago is an independent chapter of The Triple Helix, Inc., an educational 501(c)3 non-profit corporation. The Triple Helix at the University of Chicago is published twice per year and is available free of charge. Its sponsors, advisors, and The University of Chicago are not responsible for its contents. The views expressed in this journal are solely those of the respective authors.

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