Princeton Journal of Bioethics - Winter 2010

Volume XI Winter 2010-2011

PJB Princeton Journal of Bioethics

Dedicated to the discussion and contemplation of issues at the intersection of technology and society.

Vol. XI Winter 2010-2011

The Princeton Journal of Bioethics Tony Trenga ‘11 Editor-in-Chief Angela Dai ‘13 Bruce Easop ‘13 George Maliha ‘13 Joseph Park ‘13 James Williams ‘13 Alina Yang ‘13 Editorial Staff

Copyright 2010 by the Princeton Journal of Bioethics.

All rights reserved.

Cover Design: Jared Serwer ’98 Bioethics Emblem: Darryl Bledsoe ‘98

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Foreword

Technical Review Board The Technical Review Board was created to review the student writing thereby ensuring the accuracy and quality of the Journal. We would like to extend our appreciation to these professionals who donated their time and expertise to our endeavor.

Martin R. Eichelberger, MD Professor of Surgery and of Pediatrics, George Washington University; Attending Surgeon, Children’s National Medical Center, Washington, D.C. Eric Gregory, PhD Professor of Religion, Princeton University Irene Jillson, PhD Assistant Professor in the School of Nursing and Health Studies, Georgetown University Peter Singer, B.Phil Ira W. Decamp Professor of Bioethics in the University Center for Human Values, Princeton University

On behalf of our staff, I am pleased to present the Winter 2010-2011 issue of the Princeton Journal of Bioethics. The articles we have selected for this issue discuss topics such as direct-toconsumer testing (DTC) for genes associated with athleticism, the negative affects of medical reductionism on patient care, the societal responsibilities of the pharmaceutical industry, and the ethical implications of stem cell research from the Hindu perspective. We hope that you find this issue enlightening.

The articles included in the Journal are submitted by undergraduate students from around the country. With the guidance of the Technical Review Board, the Princeton Journal of Bioethics Editorial Board compiles, edits, and publishes this work. As our fine tradition of publishing the best undergraduate work in bioethics depends on student submissions, we encourage you to send us papers relevant to bioethical topics so that we may consider them for upcoming issues of the Journal.

We could not have published the Journal without the guidance of our Technical Review Board. These prominent experts ensure the accuracy and quality of our publication. They have made time in their busy schedules to help undergraduates explore the role of bioethics in our society.

Thank you for your continued support and interest in the Princeton Journal of Bioethics. We hope that the Journal provides you with new perspectives and material to ponder, debate, and discuss.

It is only through sustained dialogue and awareness that progress in bioethics can be made, and we invite you to become an active participant in this exciting and rapidly growing field.

Sincerely, Tony Trenga ‘11 Editor-in-Chief

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The Princeton Journal of Bioethics Volume XI, Fall 2010 Contents Foreword Tony Trenga ‘11 Princeton University

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Justification of the Immorality of Embryonic Stem Cell Research: A Hindu Perspec-

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Bharath Krishnamurthy ‘12 University of Virginia

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Corporate Conscience: How One Pharmaceutical Company Created A Model Where Profitability And Philanthropy Could Coexist Emma Margolin ‘10 University of Pennsylvania Medical Reductionism and Its Implications: A

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Critical Analysis of the Role of the Laboratory in Modern Medicine Rahul Rekhi ‘13 Rice University

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Implications of Direct-to-Consumer Testing for Genes Associated with Athleticism Arun Sharma ‘12 Duke University

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Justification of the Immorality of Embryonic Stem Cell Research: A Hindu Perspective Bharath Krishnamurthy ‘12 University of Virginia

The articles herein do not reflect the views of the Princeton Journal of Bioethics or its affiliates.

Stem cell research has experienced long-standing debate over its moral righteousness. Various religious philosophies have sought to determine this moral righteousness by delving into the religious texts. Surprisingly, very little documentation exists on Hinduism’s perspective on stem cell research. Upon looking at several scholarly interpretations of the Vedas (Hindu religious text), stem cell research would be rejected by Hinduism because this form of research calls for the direct destruction and interruption of life. According to the Vedas, life is seen to be at the moment of conception akin to the Catholic philosophy on life. The doctrine of ahimsa mandates that all beings lead a life of nonviolence, while the doctrine of karma refers broadly to all the acts one does throughout his or her life. Based on his or her karma, one can determine in what form one will be reborn in his or her next life (samsara). A combination of the doctrines of karma, ahimsa, and samsara indicate that Hinduism would reject stem cell research. Inarguably, stem cell research has several promising medical applications that can aid significantly in the process of unearthing potential cures to a variety of ailments. However, society must bear in mind the ethical standards that are broken in an effort to do potential good. Though this topic seems to be perpetually contentious, the Hindu perspective sheds a new light on this issue in an effort to better understand the moral and ethical considerations of stem cell research.

Hinduism, the third largest religion in the world, is the main religious philosophy practiced in the Indian subcontinent. Though by traditional definition Hinduism can be described as a religion, it is more accurately defined as a way of life (Sanātana Dharma). This “way of life” is mandated through a series of religious texts that describe certain rules by which one should abide.1 Various interpretations of these religious texts, the Vedas and the Upanishads, have shed light on the fact that Hinduism holds life to begin at the moment of conception. Hindu philosophy rests on three important doctrines—karma, ahimsa, and samsara.2 Karma is widely defined as the set of deeds, good or bad, one “collects” throughout 1 Besant, A, & Das, B. (2000). Sanatana dharama: an advanced textbook of hindu religion and ethics. Chennai, India : Theosophical Pub.House.

2 Tobis, J. S., et.al. (2008). Fundamentals of the stem cell debate. Univ of California Press.

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life. “Bad karma” is philosophically regarded as an act that transgresses basic Vedic principles. Ahimsa is the absolute principle of nonviolence – one shall not do harm to another. Samsara (literally the cycle of life), or reincarnation, is a predominantly Hindu idea that suggests a system of rebirth whereby a person’s karma dictates in what form a person is to be born in the next life.3 Grossly oversimplified, these forms are organized in a hierarchical structure of life from the level of God at the top, to inanimate objects at the bottom. One’s place in this hierarchical structure is determined by the karma one does in his or her life. Therefore logically, a person who does not practice nonviolence will attain bad karma and will be reincarnated into a form that is lower in the hierarchy. Collectively, these doctrines suggest that Hinduism is against embryonic stem cell research, because it is immoral to subject any life to harm and doing so will result in a violation of Hindu religious law.

Stem cell research, originating in the 1960s, been thought to have the potential for treatment of a wide range of diseases and disorders including cancer, diabetes and Alzheimer’s disease. Stem cell research can be performed with the use of both adult stem cells and embryonic stem cells. In adult stem cell research, adult stem cells are removed from living organisms without harming the organism directly. Therefore, Hinduism would condone stem cell research with the use of adult stem cells as ahimsa is maintained. Adult stem cells have been in the treatment of blood and bone cancers for some years. Conversely, embryonic stem cells are procured by removing the inner cell mass in the blastocyst during embryogenesis.4 Harvesting of these embryonic stem cells necessitates the destruction of the embryo in the process, which is the cause of great debate. The Center for Bioethics and Human Dignity reports that “typically, [stem cells] are derived from human embryos –often those from fertility clinics who are left over from assisted reproduction attempts.”5 Since stem cells can be manually differentiated into any type of cell, their potential is limitless in providing a possible cure to many diseases plaguing society. Current methods of embryonic stem cell procurement call for the destruction of the embryo, which begs an important question: Is the embryo considered to be an individual living entity?

According to the Vedas and the Upanishads, one cannot do harm to another. This “another” in Hinduism extends not only to human

life, but to all life (sarva-bhuta)—in fact, it is the very reason that most Hindus are vegetarian. Jerome Tobis et al. assert that “conception is held to occur after intercourse […] more specific[ally], [the time when] jiva, or individual soul, […] descends into the union of semen and menstrual blood.”6 By that logic, Hinduism would consider the beginning of life to be at the moment of conception. Any stage beyond that point is considered life, since the biological entity has a soul of its own. This idea is similar to the Roman Catholic view described by Dr. Edmund Pelligrino, Chairman of the President’s Council of Bioethics (2005-08) and founder of the Georgetown University Center for Clinical Bioethics, that “upon conception, the biological and ontological individuality of a human being is established.”7 The Roman Catholic view that life begins at the moment of conception has been well-noted in bioethical literature. The very fact that Hindu philosophy on this basic point of contention is similar in nature to that of the Roman Catholic philosophy implies that Hinduism would also consider stem cell research immoral. The notion that the entity, at the moment of conception, has individuality and is not seen as a part of the mother is a distinction that is vital to the understanding of not only the Hindu position, but also the stem cell debate as a whole. Essentially, anything that has a jiva is considered both as living and an individual.

Therefore, coupled with the doctrine of ahimsa, it would be morally wrong according to Hindu law to destroy a living entity for any reason, even if the reason is noble.

By not practicing ahimsa and destroying life, a Hindu would obtain bad karma, which would lead to a regression in the reincarnation hierarchy — the demotion from human life, which, aside from God, is the highest stage in the hierarchical structure. Hindu philosophy holds that it is every soul’s goal to be at one with God, or in other words to attain a “level” known as bramhan. According to the reincarnation doctrine, a human who has bad karma will be reborn as an entity that is further down this hierarchical structure. In other words, the jiva is further from attaining bramhan.8 Therefore, a Hindu who participates in the active destroying of embryos as a result of the current methods of practice in stem cell research would be considered to have obtained bad karma. As the Center for Bioethics and Human Dignity reported, many of these very embryos being used for research are the result of abortions, which as Dr. Pelligrino states,

3 Yevtic, P. (2006). Karma and reincarnation in hindu religion and philosophy.

Kessinger Pub. 4 An Overview of stem cell research. (n.d.). The Center for Bioethics and Human Dignity, Retrieved from <http://www.cbhd.org/stem-cell-research/overview>.

5 Ibid.

6 7 8

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Tobis, J. S., et.al.

Pelligrino, E. Testimony of edmund d. pelligrino, m.d. Commission on Human Ethics.

Yevtic, P.

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“involves complicity in the direct interruption of human life.”9 Current guidelines set forth by the Indian Council of Medical Research state that human embryonic stem cell research can be used in research efforts for the purpose of benefiting science and medicine.10 However, simply using the embryo for research purposes in an effort to benefit science and medicine would require scientists to inject these embryos with harmful strains of bacteria and viruses to test the viability of these cells subject to microbial interference. Hence, according to Hindu law, it would be immoral to harm these cells (injecting stem cells with harmful strains of bacteria or viruses), as they are living and have a jiva within them. In addition, the doctrine of ahimsa not only mandates that one not destroy but also not do any harm, termed “nonmaleficence” as described in the West by Dr. Tom Beauchamp and Dr. James Childress, Professors of Biomedical Ethics at Georgetown University and the University of Virginia, respectively.11 As such, any form of research that requires harming an animal would be prohibited. In conclusion, embryonic stem cell research is especially contested because both the procurement and the method of experimentation require harming the living entity.

Dr. Robert Paul Lanza, Chief Scientific Officer of Advanced Cell Technologies (ACT) and Adjunct Professor at the Wake Forest University School of Medicine, argues that “good actions that change the course of suffering for oneself and others are exhorted not only so that one can advance morally but because other people are worthy of beneficent deeds.”12 However, any moral code could argue that society is not allowed to decide who is worthy and who is not, another absolute principle. An embryo has no more moral significance than an adult human being, because Hinduism sees life as constant no matter the stage of life present.

Furthermore, the doctrine of ahimsa or nonmaleficence is more morally obligatory than the doctrine of beneficence as stated by Dr. Beauchamp and Dr. Childress.13 Though stem cell research can potentially lead to positive results in the efforts to cure various forms of cancer and other debilitating diseases, Hinduism contends that destroying or harming life in the process of obtaining a good result is bad karma. This is because a good result does not necessarily justify the actions necessary to achieve that

positive outcome –a non-consequentialist ethical ideal.

Utilitarian philosophy as conceived by Jeremy Bentham and John Stuart Mill would argue that “that action is best that produces the greatest good for the greatest number of people.”14 With great potential medical and scientific merits, stem cell research unarguably poses great utility for mankind. The ability not only to treat diseases –but even possibly to cure them –makes for a strong “pro-stem cell research” case. However, the utilitarian argument is devoid of important ethical considerations.

To destroy and harm life in order to save life not only ignores the moral gravity of the situation but it also seems counter-intuitive both ethically and logically. Hinduism would contend that the utility of stem cell research is morally confined as a result of the ahimsa doctrine. Therefore, utilizing available adult stem cells instead of embryonic stem cells to conduct valuable research would not only provide great benefit but would also preserve the sanctity of life.

Hinduism would not look favorably at embryonic stem cell research given the current conditions of the research being done. However, as Dr. Leon Kass, Chairman of the President’s Bioethics Committee (2001-05), asserted, “Other avenues to adult cell programming and other alternative sources are being pursued in the laboratory.”15 Hinduism would unequivocally allow stem cell research if life was not being destroyed in the process. Research efforts should be focused on unearthing new methods to isolate and harvest adult stem cells. No one can argue that stem cell research has merits that can potentially seek out the treatments to many diseases currently plaguing the world. However, Hindu research communities should tread ethical boundaries carefully bearing in mind central Hindu ethical values. A 2005 New York Times article titled “How India Reconciles Hindu Values and Biotechnology” reports, “[Hindus] subscribe to a worldly form of Hinduism - one that now proves to be infinitely adjustable to the modern era, endorsing […] biotechnology as well as India’s claim to be taken seriously as an emerging economic and scientific superpower,” suggesting that biotechnological efforts like stem cell research are commonly practiced with little regard to the Hindu values being trampled in the process.16 The same article states that the greatly renowned Hindu spiritual and political leader, Mohandas Gandhi, “accused Western medicine, along with much of modern science and

9 Pelligrino, E. 10 “Guidelines for Stem Cell Research and Therapy. (2007). Department of biotechnology & indian council of medical research. Retrieved (2010, May 20) from <http:// www.icmr.nic.in/stem_cell/stem_cell_guidelines.pdf>.

11 Beauchamp, T.L. , & Childress, J.F. (2009 ).Principles of biomedical ethics. New York, NY: Oxford University Press.

12 Lanza, R. P. (2006). Essentials of stem cell biology. Academic Press.

13 Beauchamp, T.L., & Childress, J.F.

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14 Ibid.

15 Kass, L. R. (2005, July 12). A way forward on stem cells. The Washington Post.

16 Mishra, P. (2005, August 21). How india reconciles hindu values and biotech. The New York Times, Retrieved from <http://www.nytimes.com/2005/08/21/ weekinreview/21mishra.html>.

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technology, of inflicting violence upon human nature.” As a Hindu, I cannot turn a blind eye to the destruction of life regardless of the potential beneficence of the result. As Former President George W. Bush stated in his 2001 Stem Cell Research address, “Even the most noble ends do not justify any means.”18 17

Works Cited An Overview of stem cell research. (n.d.). The Center for Bioethics and Human Dignity, Retrieved from <http:// www.cbhd.org/stem-cell-research/overview>. Beauchamp, T.L. , & Childress, J.F. (2009). Principles of biomedical ethics. New York, NY: Oxford University Press.

Pelligrino, E. Testimony of edmund d. pelligrino, m.d. Commission on Human Ethics.

Tobis, J. S., et.al. (2008). Fundamentals of the stem cell debate. Univ of California Press.

Yevtic, Paul. (2006). Karma and reincarnation in hindu religion and philosophy. Kessinger Pub.

Besant, A, & Das, B. (2000). Sanatana dharama: an advanced textbook of hindu religion and ethics. Chennai, India : Theosophical Pub. House.

Bush, G.W. (2001). Text of president george w. bush’s statement on stem cell research. Office of the Press Secretary , Retrieved from <http:// www.whitehouse.org/news/releases/2001/08>.

“Guidelines for Stem Cell Research and Therapy.

(2007). Department of biotechnolog y & indian council of medical research. Retrieved (2010, May 20) from <http:// www.icmr.nic.in/stem_cell/stem_cell_guidelines.pdf>.

Kass, L. R. (2005, July 12). A way forward on stem cells. The Washington Post.

Lanza, R. P. (2006). Essentials of stem cell biology. Academic Press.

Mishra, P. (2005, August 21). How india reconciles hindu values and biotech. The New York Times, Retrieved from <http:// www.nytimes.com/2005/08/21/weekinreview/21mishra. html>.

17 Ibid.

18 Bush, G.W. (2001). Text of president george w. bush’s statement on stem cell research. Office of the Press Secretary , Retrieved from <http://www.whitehouse.org/news/releases/2001/08>.

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Corporate Conscience: How One Pharmaceutical Company Created A Model Where Profitability And Philanthropy Could Coexist Emma Margolin ‘10 University of Pennsylvania The benefits of the modern medical landscape, comprised of sophisticated technology, generous funding, and an unprecedented availability of information, have yet to reach all members of the global community equally. While the wealthy can expect to live free from the perils of preventable disease, those in the poorest nations suffer blindness, deformation, and premature death.

River blindness is one of the 15 illnesses the World Health Organization characterizes as “neglected tropical diseases.” While pharmaceutical companies have had the opportunity to develop medical solutions for some of these diseases, the people most in need of them are unable to afford them due to the attached costs of research and development. Neglected tropical diseases keep people in developing nations trapped in a cycle of poverty, with no help in sight.

In 1987, the pharmaceutical giant Merck & Co. redefined the stakes of corporate philanthropy by donating the preventative treatment for river blindness to victims in West Africa. In choosing to pursue a moral imperative to help disease-ridden communities over the professional obligation to act in the shareholders’ best interests, Merck launched a revolution in the network of global health. Since then, other companies have created similar donation programs, while non-government organizations and governments alike have adopted more aggressive tactics to eradicate neglected diseases.

In 1978, in the suburban town of Rahway, New Jersey, Dr. William C. Campbell took a first step toward changing the role pharmaceutical magnates would play in the network of global health. While he and his team of research scientists at Merck & Company were trying to find what Campbell called “the best drug ever” for treating parasitic worm diseases in domestic cattle, 18 million people in the water-lands of West Africa were suffering from onchocerciasis, an illness usually referred to as “river blindness.”1 After years of research, in the peculiar way serendipity and science can interact, Dr. Campbell found himself face-to-face both with the solution to the cattle problem he was looking for, and with the groundbreaking discovery made along the way—Mectizan, a drug that 1

Useem, Michael, The Leadership Moment, (New York: Three Rivers Press, 1998) 14.

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could bring relief to the millions at risk of developing river blindness.

Such a medical breakthrough might have seemed the greatest hurdle, yet as he was soon to discover, Dr. Campbell and Merck›s most profound challenge in the years ahead would be to address how to actually get that relief to the villagers of West Africa. In “developing” nations, in parts of Africa, Latin America, and the Middle East, where river blindness runs rampant, profound poverty prevents sufferers from purchasing vaccines of any kind at what is considered their market value in the “developed” world. The effects of river blindness and similar parasitic diseases in poverty-stricken areas are cyclical, since these diseases blind, disfigure, or otherwise handicap their victims. Once infection sets in, it becomes practically impossible for people to pull themselves out of destitution.

River blindness is just one of the 15 diseases the World Health Organization characterizes as “neglected tropical diseases.” “Neglected” has a dual meaning, experts point out. According to Ashly Smolyn, development program officer at the Sabin Vaccine Institute, a non-profit vaccine research and development organization, “these diseases are called ‘neglected’ because they have received less attention and funding than more wellknown diseases, such as HIV/AIDS, malaria, and tuberculosis; [but] they also primarily infect people who are ‘neglected’ in society—the poorest of the poor.”2 Because neglected tropical diseases only affect those unable to pay for a vaccine, drug developers have had little incentive to focus on their eradication. Pharmaceutical corporations rely on profits just as any other company would, and the philanthropic undertaking required to target these diseases can cost an onerous amount of money, time, resources, and status points. Yet when Dr. Campbell worked to develop a river blindness vaccine, he effectively, albeit unknowingly, broke ground on the bridge that would connect corporate profitability with humanitarian aid. His determination, alongside the efforts of so many other Merck employees, to halt the proliferation of river blindness represents a case study in pharmacological philanthropy, as well as a reflection of the ethical dilemma facing pharmaceutical company executives: how can medicine address both the profits and the patients?

River Blindness and the Absent Response River blindness, first medically identified in 1893, is caused by the parasitic worm Onchocerca volvulus. The worm is transmitted through 2

Smolyn, Ashly, Personal interview. 17 December 2009.

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the bites of infected black flies that carry the parasite’s immature larvae.

Once the black flies bite, the larvae penetrate the human body, where they mature into adult worms. When they die, they cause a variety of conditions, including blindness, skin rashes, lesions, and intense itching.

According to the Carter Center River Blindness Program, in some parts of Africa, such as Ethiopia, Nigeria, Angola, and Malawi, each person is bitten by black flies as many as 20,000 times each year.4 As a consequence, in these endemic areas, half of the residents could expect to become blind before death.

Dr. William Foege, health policy fellow and former executive director of the Carter Center, a not-for-profit human rights organization, witnessed the effects of river blindness firsthand while living in a Nigerian village for six months in 1965. During that time, he was struck by how dominating the symptoms of this disease could be.

“If you sat around with people at night, you would see that they were continuously scratching. And you took on some of their habits, even if you weren’t itching,” recounts Dr. Foege. “I didn’t realize at first that they were itching because of the larvae of onchocerca. The same parasitic larvae that were leading to blindness were all over the body.”5 During the 1970s, 85 million people were at risk of acquiring river blindness in 35 developing countries.6 Neither vaccine nor treatment existed to protect those most vulnerable. Yet perhaps even more problematic than the lack of a medical solution was the fact that should one arise, the prospect of its distribution to those in need was slight. In areas where the illness was prominent, sufferers could not afford to purchase a miracle drug, even if its cost were comparatively modest by developed-world standards. Simply put, there was no global infrastructure capable of developing and distributing a vaccine that was not based on direct compensation of the drug developer.

The challenges facing river blindness victims resound throughout the entire class of neglected tropical diseases, explains Smolyn. Globally, neglected tropical illnesses affect over 1.4 billion people, most of whom live on less than $1.25 per day.7 Victims, thus, have no chance of purchasing preventative treatment, at any price.

Considering the significant costs and internal resources that go into 3

3 World Health Organization. 2010. 18 October 2010 <http://www.who.int/en/>.

4 The Carter Center. 2010. 18 October 2010 <http://www.cartercenter.org/health/river_blindness/ index.html>.

5 Foege, William. Personal interview. 14 December 2009.

6 Useem 14.

7 Smolyn 2009.

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lab research, clinical studies, field trials, and distribution, CEOs and shareholders of pharmaceutical companies have for decades lacked the necessary incentive to voluntarily absorb those costs for a drug for which there was little prospect of being paid. Ken Gustavsen, director of Merck’s global donations program, explains that today, the estimates for bringing each new drug to market range between about $800 million and $1 billion.8 Undoubtedly, that estimate was different while Dr. Campbell was working on a potential river blindness vaccine in the Merck laboratories during the late 1970s, but, “suffice it say,” as Gustavsen puts it, “it would have cost a lot of money.”

Merck

For the last six years, Gustavsen has served as director of Merck’s Mectizan Donation Program, the first of its kind in terms of global pharmaceutical donations. The program began in 1987, when the company decided to give away Mectizan (the drug created in Dr. Campbell’s laboratory that was found, somewhat unintentionally, to be an effective preventative treatment for river blindness).

Such a groundbreaking program could only arise out of a company with a deep-seated humanitarian culture, asserts Gustavsen. In fact, the approach of working toward bettering human health dates back to the beginning of the organization itself. As Merck personnel tell the story, the key is in the order of the thoughts: if you do something valuable, you will be rewarded.

“We have a famous quote from the modern day founder of Merck, George Merck,” recounts Gustavsen. “We hear it all the time, and so we kind of get tired of it. But, it’s a nice quote: ‘we try never to forget that medicine is for the patients and not for the profits, and that if we put the patients first, the profits end up following.’”9 No one familiar with Merck’s revenues would argue the latter half of George Merck’s words. Touching as the quote may be, Merck has kept a firm grasp on its powerful status within the pharmaceutical industry, a position not easily maintained without thinking about money every now and again. Even in the bowels of a crippling recession, Merck’s total revenues still managed to increase by 2.1% to € 7,747 million, or roughly $10.8 billion, in 2009.10 8 Gustavsen, Ken. Personal interview. 4 December 2009.

9 Gustavsen 2009.

10 Merck. 2010. 21 October 2010. <http://merck.online-report.eu/2009/ar/managementreport/ financialpositionandresultsofoperations/businessdevelopment.html>

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Yet while the company has proven to make sure the “profits end up following,” it has also built a solid reputation for considering the first half of the equation: the patients. Prior to the Mectizan Donation Program, Merck’s philanthropic exploits have included the Merck Company Foundation, established in 1957 to support nonprofit charitable organizations, and the Office of Corporate Responsibility, which guides the strategic direction of the company’s philanthropic activities, as well as coordinates Merck’s disaster response efforts.11 The Mectizan Donation Program, however, was an unparalleled philanthropic endeavor, within both company and pharmaceutical history.

The Development of Mectizan

For Dr. Roy Vagelos, in particular, the words of George Merck were more than flowery rhetoric. Under his direction, Merck spent almost $1 billion on new-product research between 1975 and 1978, much of it going to highly paid scientists, who were encouraged to follow their instincts on projects with the potential to reduce human suffering.12 As laboratory director, part of Dr. Vagelos’s job was to review and recommend the most promising prospects for development from among thousands proposed. His decisions depended on two factors: medical need and the likelihood that a drug or vaccine would actually respond to that need.

While he also had the professional obligation of ensuring returns to Merck shareholders, Dr. Vagelos asserts that he “was always more concerned about the number of patients who could benefit from [the company’s] work.”13

Dr. Vagelos was known for giving his scientists the creative freedom to take their research as far as it could go. Among those research scientists given the license to apply their scientific acumen to global health issues was Dr. William Campbell.

In the 1970s, Dr. Campbell was conducting veterinary research, hoping to create a drug that could treat parasitic worm diseases in domestic animals. He was operating on the assumption that the cure to parasitic disease lay in naturally occurring bacteria. This research was, admittedly, intended to yield a dependable money-maker for Merck.

“In looking at thousands of bacteria,” says Dr. Campbell, “the objective was to preserve and strengthen Merck’s position in the market

for [veterinary worm] drugs.”14 He adds that his research team “also had the objective of finding the best-ever drug for combating worm diseases in people,” but recognized that Merck at the time had very little involvement in the “worm Market” for human medicine.

To conduct his research, Dr. Campbell and his colleagues tested hundreds of thousands of bacteria collected around the world, with the hope of finding just one capable of ridding test mice of parasitic infection.

By 1978, after years of work, Dr. Campbell discovered that a tiny microbe, improbably recovered from a golf course near the Japanese city of Ito, cured an infected mouse by ridding it entirely of parasitic worms. From this bacterium, Dr. Campbell developed the powerful and, as it turned out, widely used veterinary drug, ivermectin.

As intended, ivermectin was very good for business.

“The company made a lot of money with ivermectin in veterinary medicine,” recalls Dr. Campbell. But “the potential for ivermectin in river blindness was seen only after we had discovered invermectin as a powerful drug for treating worm diseases in horses.”15 Since Dr. Campbell had always been especially interested in human parasitic infections, it was easy for him to realize that the worm in horses was related to the worm that causes river blindness in people. Soon thereafter, Dr. Campbell found himself in a position to make the company executives aware of that potential for use in human medicine.

With Dr. Vagelos’s blessing, Campbell could move forward with his research, despite the prospect of incurring some as yet unknown additional costs.

“The development of a special formulation for humans and the safety testing for human use cost the company many millions of dollars,” remembers Dr. Campbell. Nevertheless, he emphasizes, “support was unwavering.”16

Though part of his job was to act in Merck’s best economic interests, Dr. Vagelos says he “never turned away from a potentially important product because of costs.”17 He firmly believed that Merck could always find a way to deliver the medicines to the people who needed them.

Dr. Vagelos gave Campbell the necessary internal authorization to proceed with his work, which turned into a lengthy endeavor. Nearly a decade later, that work finally paid off.

11 Philanthropy at Merck. 2008. 21 October 2010. <http://www.merck.com/corporate-responsibility/docs/philanthropy_at_merck.pdf>.

12 Useem 16.

13 Vagelos. P. Roy. Personal interview. 5 December 2009.

14 15 16 17

12

Campbell, William. Personal interview. 8 December 2009.

Campbell 2009.

Campbell 2009.

Vagelos 2009.

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Now the question facing Dr. Vagelos became, “how can Merck make money,” states Dr. Foege. “And, of course, he concluded, he couldn’t.”23

“After a few years of research in the lab, followed by seven years of clinical studies and field trials in West Africa, [Merck scientists] determined that the drug was safe and effective for use in humans for river blindness,” states Gustavsen.18 Merck won regulatory approval for the drug first in France, and then in other countries.

The research alone was a sizeable investment for Merck in terms of internal resources. But also on the line was Merck’s reputation in the veterinary business. Merck executives were primarily concerned with potentially dangerous side effects and deaths, which are usually not experienced equally in human and animal test subjects.

“If you have a death every 100,000 people,” explains Dr. Foege, “by the time you get up to a few million people, you have so many deaths that this turns out to be a real problem.”19 Had ivermectin proven to be dangerous in its human application, Merck might have been forced to take it off the market, even for its veterinary uses, at a significant financial cost to the company. Still, the research went forward.

“The benefits of finding a new treatment for [river blindness] outweighed the risks of anything negative that might have been found,” states Gustavsen.20 Ivermectin’s human application was renamed Mectizan. Luckily for Merck and its reputation, the clinical trials revealed no harmful side effects.

“This had to be one of the safest drugs ever made,” states Dr. Foege, who could vividly recall the severe itching he observed while living in Nigeria. The relief experienced by those participating in the trials was overwhelming.

“For some, it was the first time in their life they could remember not itching,” reflects Dr. Foege. “I mean, it’s very dramatic.”21 Dr. Vagelos, who had presided over the development of a number of successful drugs, was similarly enthused.

“We had discovered a near magical medicine for this problem that could benefit about 100 million people who were at risk of losing their sight,” Dr. Vagelos recalls.22 He had already invested millions of Merck’s resources, as well as risked the company’s reputation to develop Mectizan, so his sense of accomplishment was likely matched by his feeling of relief.

The Birth of the Mectizan Donation Program

When the development program for Mectizan was completed, Merck entertained several methods for delivering the drug to the people who needed it. First, they considered selling it at a very low price. This option was crushed by the central problem defining neglected tropical diseases.

“That [option] would not work because these were among the poorest people in the world, and they couldn’t afford the medicine at 10 cents per year,” states Dr. Vagelos.24

Next, Merck executives tried to convince West-African governments to purchase the drug for their citizens. But government officials claimed they could not even afford food for their people, let alone a vaccine.

Quickly running out of options, Dr. Vagelos turned to the WHO, which had been instrumental in the 1967 global smallpox eradication by contributing $2.4 million annually to the effort. Unfortunately, this time, according to Dr. Foege, “things didn’t work out.”25 The organization had neither the time nor the money to underwrite the distribution of Mectizan.

Finally, with dwindling hope, Dr. Vagelos turned to the U.S. government for support. He offered the United States Agency for International Development (USAID) a free supply of Mectizan in exchange for the organization’s resources to issue contracts for other firms to physically transport and distribute the drug. USAID said no.

“I had a chance years later to talk to the person who was head of AID at the time,” reveals Dr. Foege, “and I asked him why they turned it down. And he said we were just too busy. Which is interesting.”26 It was interesting, considering USAID has been the principal U.S. agency to extend assistance to countries recovering from disaster, escaping poverty, or engaging in democratic reforms since 1961. If AID could not handle the Mectizan distribution, who could?

The issue was not that the U.S. government refused to acknowl-

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edge the difficulties of treating neglected tropical diseases. Rather, the problem was that the steps taken by the government were, at best, insufficient, at worst, ineffectual.

Within the pharmaceutical industry, drugs with uneconomic markets are labeled “orphans.” Nobody, it seemed, wanted to own responsibility for Mectizan. Prior to the completion of Mectizan, however, the U.S. government had taken steps to redress the obstacles facing orphan drugs, having passed the Orphan Drug Act (ODA) in 1983. The ODA is meant to encourage pharmaceutical companies to develop drugs for diseases that have a small market. Under the law, companies that develop such a drug may sell it without competition for seven years, and may get clinical trial tax incentives, most likely in the form of tax holidays or deductions.

Yet these orphan drug laws were primarily enacted to promote production of drugs for rare diseases affecting domestic markets, not to address the lack of medicine in the developing world. According to a report by a team of international research scientists, Stefano Villa, Amelia Compagni, and Michael R. Reich, orphan drug legislation in most countries does not even specifically mention tropical diseases, illustrating the ODA’s lack of effectiveness in making neglected diseases a global concern.27 With insufficient global health infrastructure, Merck was left with the possibility that Mectizan would sit on the shelf, unused. Shelving Mectizan would have hurt the company’s morale, as well as damaged Dr. Vagelos’s reputation.

“Since it was a unique therapy, and there was not something else out there that patients could access, it would have been irresponsible to have had Merck do research and develop something that they knew was safe and effective and was the only thing out there for patients to get,” reveals Gustavsen. “Imagine what the response would have been if [Dr. Vagelos] said to the research guys, ok, good job, but we can’t sell that, so put it back on the shelf.”28 As Dr. Vagelos remembers it, putting the Mectizan project to rest “was not an acceptable answer.” So, he decided that Merck would contribute the drug for free to anyone in the world for as long as it was needed.

“That solved the patient problem and that made a lot of Merck people very happy,” states Dr. Vagelos.29 In 1987, Merck formed the Mectizan Expert Committee, a group

of public health experts, to formulate guidelines, select parties for distribution, and compile medical records of patients receiving the vaccine.

Dr. Foege was selected to chair the committee, challenged with the dual responsibility of distributing Mectizan and protecting Merck from public criticism.

“We decided to have the Mectizan Expert Committee as a way of separating Merck from the actual operations,” explains Dr. Foege. “If you had people from Africa coming to Roy Vagelos asking for the drug, Merck would have a hard time turning them down because it just wouldn’t be good publicity.” The Expert Committee was created “as an interface.”

The Mectizan Expert Committee started working with mission groups, foundations, and non-profit organizations that actually work in the field to distribute the drug. They were trying to create an organized system for eliciting and entertaining proposals from non-government organizations for Mectizan. Naturally, there were certain requirements these organizations had to meet before receiving the vaccine from the committee. The main stipulations were that every organization’s request for the drug had to show how they were going to use it, how many people were going to get it, how they were going to store it, and how they were going to maintain security over it. Additionally, the entire plan had to go through the ministry of health of the countries where the disease existed, so that the ministry would know what was happening in its country.

The committee members were quite pleased with the communication network they created between Merck, developing countries, and NGO workers in the field.

“I think the system worked quite well,” recounts Dr. Foege. “We had a good committee. We kept changing the people on the committee, but they were people interested in the problem, many of them having had great experiences with onchocerciasis.” He continues, “We would meet about every three months, go through the applications, approve them, and try to figure out what other problems we were facing.”

While the Mectizan Expert Committee was originally created to put some distance between the donation program and the company, Merck personnel have since assumed a shared responsibility for the program’s success.

“It’s important to remember that though it was Dr. Vagelos who made the decision to donate Mectizan for free, it’s a corporate commitment,” asserts Gustavsen. “It was not a personal commitment, and it’s not a commitment that changes with stock prices and CEOs. It’s a commit-

16

17

27 Compagni, Amelia, & Reich, Michael R. & Villa, Stefano. (2008). Orphan Drug Legislation: Lessons for Neglected Tropical Diseases. International Journal of Health Planning and Management. doi: 10.1002/hpm.930.

28 Gustavsen 2009.

29 Vagelos 2009.

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ment that the company makes and that we still live up to.”30 The Snowball Effect

In 1991, four years after the Mectizan Donation Program began, USAID, which had earlier denied Dr. Vagelos’s request for backing, provided $2.5 million for distribution assistance. It seemed that overnight the program had transformed into the most popular group in the school of global health, one that everyone wanted to join.

“Once the program got off the ground, there were lots of people who wanted to be part of it,” explains Dr. Foege. “It’s harder to start these things than to get people interested once they’re going.”31 With growing interest and funding, the program was soon poised to expand.

By the late 1990s, Dr. Foege was still chairing the Mectizan Expert Committee. During one of the committee’s regular meetings in France, the WHO’s Eric Ottesen reported on a successful study done on the use of Mectizan and ablbendazole (another treatment for worm infestations) together in the treatment of lymphatic filariasis, a different neglected tropical disease.

The primary manufacturer of albendazole was another pharmaceutical giant, Smith Kline Beecham, which would later merge to become GlaxoSmithKline. In order to incorporate treatment for lymphatic filariasis into the Mectizan Donation Program, someone very high up in the management of Smith Kline Beecham would have to authorize a free contribution of albendazole, in much the same way Dr. Vagelos did with Mectizan.

“Someone asked, does anyone know someone at Smith Kline Beecham high enough up that they could authorize a gift of the drug so we could try it with larger groups,” recalls Dr. Foege. “No one did, but we broke then for a reception and dinner, and we were all talking about this exciting new development—one more thing in global health that could be done.” 32 The next morning, Dr. Foege got quite an unexpected, albeit opportune, phone call. “It’s now ten o’clock in the morning in France, and a person puts a note in front of me that Jimmy Carter is on the phone, would I take the call,” Foege retells with ease. “Which I did.”

The night before, President Carter had dined with Jan Leschley, 30 31 32

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former tennis champion of Denmark, and the current CEO of Smith Kline Beecham. During their meal, Leschley had intimated how impressed he was with Merck’s Mectizan Donation Program, and he had asked the President for some ideas that would allow Smith Kline Beecham to launch a similar initiative.

“And Carter said, he couldn’t think of anything right off, but now he was calling me asking, do you know of anything they could do? Talk about serendipity,” states Dr. Foege, with genuine and what seems unfading enthusiasm.

Smith Kline Beecham agreed to provide albendazole for the lymphatic filariasis program. After some additional research on Mectizan and lymphatic filariasis, Merck extended the Mectizan Donation Program to include vaccines for that illness in 1998. Amazingly, reflects Dr. Foege, “everything sort of came together.”

Pharmacological Philanthropy and the New Network of Global Health

In terms of magnitude, the Mectizan Donation Program has grown to currently donate about $600 million worth of vaccines every year, reaching about 100 million people. Merck has also developed the Merck Medical Outreach Program, which works with a set of six main non-profit organizations to donate medicine and vaccines to the developing world.

This program usually donates usually between $50 and $100 million worth of product per year.

But Merck’s success has grown outside of the company’s boundaries as well, inspiring other pharmaceutical corporations to develop their own donation programs. For example, 10 years ago, Pfizer announced an initiative to donate antibiotics for trachoma, another tropical disease. GlaxoSmithKline also continues its partnership with Merck for the lymphatic filariasis program.

“A lot of those companies have acknowledged the inspirational role both in concept and in practice in terms of consulting with Merck,” states Gustavsen.33

The main commonality recurring in each of these pharmaceutical donation programs, however, is the collaborative partnership of many different groups. There are some of the usual suspects across all the programs.

The World Health Organization is usually involved either in implementation or in a type of advisory capacity. From a funding standpoint, there are groups like the Bill and Melinda Gates Foundation, which finances the 33

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Sabin Vaccine Institute, and the Carter Center.

“The basic model,” emphasizes Gustavsen, is “one of each element of the partnership bringing their strengths to the table, but agreeing on a common objective, be it disease control, or disease elimination, or serving a certain country.”34

Pharmaceutical companies have devised these donation programs specifically for diseases that only affect people in the developing world.

Surprisingly, expanding these donation programs to include more common diseases would actually make them more difficult to sustain, even though common diseases can be treated with fewer resources.

“The reason you can take a different approach for a tropical disease is that in a way, you don’t have to worry about the market potential, because it just isn’t there,” states Gustavsen. “Whereas with a drug for high cholesterol or HIV, or something like that, in a way the decision is a little more complicated, because you’re thinking well yeah, there are people in Africa who are affected by it, but then there are also people in New Jersey who are affected by it.”

Targeting only neglected tropical diseases actually relieves pharmaceutical companies from the pressure of incorporating every new drug developed into some kind of donation program. That strategy would be completely unsustainable from a business standpoint.

“A pharmaceutical company would cease to exist in about 12 months if they decided to do that,” explains Gustavsen, “because in those cases you have to come up with a market-based solution that’s going to be sustainable in the developed world and in the developing world.”35 There are some critics who argue against pharmaceutical donations entirely, claiming that real improvement to global health needs to come in the form of a market-based solution. But when the issue is a life-altering disease, such as river blindness, waiting for a long-term solution can mean profound suffering for millions.

“There’s a great cartoon I saw once in the New Yorker that had a patient going to the desk in a hospital, and the guy at the desk says, ‘Oh, please have a seat until a market-based solution is developed,’” quips Gustavsen. “Obviously, it can take decades or centuries for such a solution to emerge.”36 The more common opinion among experts, however, is that to

move forward with building a global health infrastructure, there should be continued joint efforts on part of pharmaceutical companies, privately funded organizations, and government legislation.

“You have to do both,” states Gustavsen, in reference to either continuing donation programs, or instead pushing for legislation reform. “I think all of the partners, and all of the companies, all of the actors, like the World Health Organization, the World Bank, and everything realize that you have to do both.”37 The U.S. government is now more attuned to neglected tropical diseases and the flawed orphan drug laws. President Obama recently named neglected tropical disease control and elimination as one of four key pillars in his Global Health Initiative (GHI.)38 Targeting which diseases to combat has also become more sophisticated in the last 15 years. Government efforts tend to target diseases that are the biggest problems, meaning those that cause the most people to suffer or die.

“Until 1993, it was hard to separate those two (suffering and dying,”) explains Dr. Foege. “Then in 1993, the World Bank came out with the Disability Adjusted Life Years (DALYs,) which allows for suffering and death to be put into a single number. And that made it a little easier for (governments) to compare.”39 While mortality rates used to be the only standard to describe health, DALYs can tabulate the number of healthy years lost to injury, illness, and premature death. Now, this new unit allows for governments to track the effects of certain diseases that had previously been overlooked for not directly raising mortality rates.

Overall, the improvement in global health infrastructure in the last few years has been staggering, these experts point out.

“The environment in global health has moved so fast in ten years,” reflects Dr. Foege. “There are a lot of indications, but one of them is that there are now 200 global health programs in this country at institutions of higher learning. A decade ago, I’ll bet there weren’t 20.”40 Nevertheless, the global network has a long way to go before achieving complete eradication of neglected diseases.

“Public health has been improved throughout the world through the contributions of the pharmaceutical industry and the major contribu-

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tions of many foundations,” states Dr. Vagelos. “But there are plenty of areas that can still be improved.”41 Dr. Foege sees two enduring problems. One is the actual delivery of medical tools, meaning vaccines and treatments that impoverished sufferers cannot access. The other problem is what some people call “the brain drain,” the trend of medically trained professionals leaving their countries and taking their skills somewhere else.

A potential solution to the first problem would be a concerted effort by the WHO and others to encourage pharmaceutical companies to provide new medical tools, and to send some of their best managers to developing countries, in order to figure out how best to deliver those tools.

For the second, Dr. Foege offers something a little more inspired and a lot more challenging.

“We should graduate people with more than a diploma. We should graduate people with a diploma and a warranty in global health, so that students can return to their countries and actually use the skills and knowledge they’ve acquired,” states Dr. Foege.42 Despite these challenges on the horizon, the global health landscape has definitely transformed since Dr. Campbell first discovered his powerful, parasite-killing bacterium deep within Merck’s New Jersey laboratory.

“I think the last decade has just changed everything, from research, to delivery, to the attitude of people,” imparts Dr. Foege, who had a chance to go back to Africa for the 250 millionth distribution of Mectizan in Tanzania. “I am very optimistic about what’s happening in global health.”

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Works Cited Campbell, W. Personal interview. 8 December 2009.

The Carter Center. 2010. 18 October 2010 <http://www.cartercenter.org/ health/river_blindness/index.html>.

Compagni, A., Reich, M.R., Villa, S. 2008. Orphan Drug Legislation: Lessons for Neglected Tropical Diseases. International Journal of Health Planning and Management. doi: 10.1002/hpm.930 Foege, W. Personal interview. 14 December 2009.

Gustavsen, K. Personal interview. 4 December 2009.

Merck. 2010. 21 October 2010. <http://merck.online-report.eu/2009/ar/ managementreport/financialpositionandresultsofoperations/businessdevelopment.html>.

Philanthropy at Merck. 2008. 21 October 2010. <http://www.merck.com/ corporate-responsibility/docs/philanthropy_at_merck.pdf>.

Smolyn, A. Personal interview. 17 December 2009.

Useem, M. The Leadership Moment. New York: Three Rivers Press, 1998, 14.

Vagelos, P. R. Personal interview. 5 December 2009.

World Health Organization. 2010. 18 October 2010 <http://www.who. int/en/>.

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Foege 2009.

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Medical Reductionism and Its Implications: A Critical Analysis of the Role of the Laboratory in Modern Medicine Rahul Rekhi ‘13 Rice University With the relentless pace at which technology and scientific advancements have come to dominate the medical landscape, it is, perhaps, inevitable that the “fuzzy” logic of the individual be eclipsed by the hard certainty of observational rationality. In recent years, however, the extent of this shrouding has appeared to accelerate far beyond the bounds of tolerability, and it is becoming increasingly clear that the admittedly-remarkable gains of the laboratory have not come without terrible cost—namely, the dramatically diminished presence of the human element in medical decision-making. Whether or not this cost offsets entirely the aforementioned progress remains in contention; to answer this question, this paper explores the effects of 21st century mechanistic reductionism with regards to the clinical efficacy of modern medicine.

From shamanistic herbalism and the balancing of the four humors to sheer pharmaceutical (and laboratory-based) innovation, the study of medicine has undergone a gradual evolution, as the generational refinement of our physiological knowledge has superseded the observational approach of our ancestors. Indeed, the maturation of the medical practice has brought about a fundamental transformation of its essence—less art, more science, mechanism trumping vitalism. This “progress,” however, has not come without cost; the rapid advancement of our command over the physiological realm of our existence is matched only by the stagnation in our understanding of its phenomenological consequences. Although the development of a fundamentally reductionist medical perspective has undoubtedly augmented the capability of modern medicine in the realm of acute care, in its ascension, we have forgotten the human element so deeply tantamount to the ultimate goal of the physician—to heal.

Primarily, it is important to note that bemoaning the infiltration of raw science in the modern medical practice is not an act restricted to Luddites alone; even the most entrenched of Big Science’s supporters will attest that the growing influence of the laboratory has had tremendous implications for doctor-patient relations. After all, in the Age of the MRI, 24

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the once-nebulous—and often-messy—diagnostic process has been all but transcended, for, as suggested by Dr. Drew Leder of Loyola College in Maryland, “the ambiguous complaints of the patient…are reorganized into a medically defined world”1. Such a simplification is hardly a radical concept; after all, breaking down a complicated problem into a more sterile—and consequently, more easily solved—model is the hallmark of engineering, scientific, and mathematical practice. While reducing the chaotic equilibrium of stresses and strains in a truss to a collection of numbers is an entirely innocuous—and undoubtedly effective—process, the same methods cannot be applied when performing medical procedures on one’s fellow man. Indeed, such simplification is innately divisive—a step conspicuously removed from the humanistic approach to medicine—for “the physiological worldview in which the modern physician is trained involves a language, a style of thought, and a set of categories which differ markedly from those of the suffering patient”2. With little to no medical expertise to guide him, the average patient is simply lost within the flood of jargon and technical sophistry that embodies the contemporary approach. In this way, the individual role of the patient has been incrementally diminished; indeed, according to Dr. Abraham Fuks, former Dean of Medicine at McGill University, “the patient’s body has become superfluous to the molecular physician; now not simply open to the medical gaze, but rather completely transparent”3. This is, of course, not to say that the mechanistic foundation to modern medicine only inhibits our ability to cure—in fact, “this shift… to a focus on underlying disease mechanisms has had enormously beneficial results,” particularly in the treatment of acute disease4. Ultimately, few would contest that such advancements as the discovery and use of antibiotics—medical miracles in their own right—have brought about veritable revolutions in the world of health care, saving millions of lives along the way. At the same time, however, such advancement is not without a significant price; after all, “many of the widely-recognized failures of modern medicine—depersonalized treatment, overreliance on medical technologies, non-compliance on the part of patients—relate to this eradication of the patient’s voice, this neglect of illness in favor of disease”5. It is telling that the primary patient complaint, month after month, year after year, is that physicians “don’t listen.” And that is the great paradox of modern 1 Leder, D. “The Experience of Pain and its Clinical Implications,” in The Ethics of Diagnosis, José Luis Peset and Diego Gracia, eds. (Amsterdam, Neth: Kluwer Academic Publishers 1992): 95.

2 Leder, 1992, 96.

3 Ibid.

4 Ibid.

5 Ibid.

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medicine—the more robust our ability to treat becomes, the more we struggle to heal.

But the onset of a mechanistic approach to medicine hasn’t only hastened the atrophy of patient-focused care through indirect means. In many cases, the perceived invulnerability of this approach in regards to improving care has caused many in the medical profession to overlook— and even disregard—the critical role of doctor-patient interactions in the healing process. After all, “technical treatments” are not the only components of the road to recovery which possess “therapeutic efficacy: the doctor-patient relationship, even the process of diagnosis itself, manifests a power to relieve suffering”6. And lest we forget, “the world of physiological diagnosis is not identical to the world of the suffering patient”; a doctor’s explanation of, say, an inflamed disc does little to alleviate its associated pain7. Rather, such a staunchly biological perspective can serve to weaken, or even sever, the all important—and powerfully curative—physicianpatient relationship, shrouding a benign offering of aid in a whirlwind of methodological wizardry. One need go no farther for evidence of such an effect than the heartbreaking story of Lia Lee of the Hmong, whose bout with severe epilepsy was unduly complicated by the profound culture clash between her physicians and her parents8. In the end, the inability of Lia’s doctors to relinquish their black-and-white, purely scientific interpretation of Lia’s condition—unable to reconcile their understanding of the situation with that of her Hmong family—left poor Lia crippled by an otherwise likely-manageable affliction9. To place the blame for the outcome of that tragic case entirely upon the shoulders of the physicians involved is both unfair and simply incorrect. However, few would contest that a better understanding of the “messy individuality” of the Hmong might have mitigated the situation, producing a less taxing outcome for all parties involved10. But that’s not all. Indeed, for all its Baconian soundness, both its flashes of scientific brilliance and technical marvel, “the physiological worldview” doesn’t just “omi[t] certain experiential concerns; more pointedly, it can serve directly to obscure them”11. For example, the conception of life not as an unfettered line between beginning and end, but as “death (and birth) intersect[ing] the line throughout” is crucial to understanding

the nature of traumatic medical experiences, such as that of Donald “Dax” Cowart12. After receiving life-threatening burns from a gas-leak-fueled explosion, Dax endured an excruciatingly painful regimen—including having his open burn wounds being washed with bleach—for weeks on end against his consent, in an audacious effort by his physician to save his life.

Now, if one’s training is entirely grounded in the biological realm, then it is only natural to view life in an absolute sense—the beating of the heart, the expansion of the lungs, the conducting of neuronal signals to the brain—as did Dax’s doctor. It is only when one endeavors to truly understand his patient—“whose very uniqueness [once] served as a means of explicating the mysteries of illness”—and not just the illness that plagues him can such spiritual abstraction be harnessed in the effort to heal13. Certainly, it’s not far-fetched to conceive that such empathy could have entirely recolored Dax’s experience. Similarly, it is telling that even the fundamental language of modern medicine is innately binary; a patient, once the epitome of human individuality, is now either dead or alive, normal or deviant, healthy or ill. Curing a disease, then, becomes akin to a fixing a faulty tire—patch it up, and it’s as good as new. Such a perspective is, however, reductionist to a downright dangerous extent; we are, after all, as much a conglomerate of lived experiences as living cells.

But the weaknesses of the mechanistic approach—and its tendency to engender willful ignorance of societal or personal factors in patient care—are not limited to the cases of the extreme (if such tragedies can be euphemized as such). Consider obesity. Based on both “intuition” and the message propagated by public official and media alike, most would readily agree that an obesity “epidemic”—engendered by the slothfulness that the 21st century lifestyle entails—has gripped the nation, threatening the health quality of future Americans for decades to come. Indeed, such an explanation appeals to our growing need for a biological cause that is proximal to the everyday oscillations in human health—after all, such a “causality is clearly understood in mechanistic terms”14. But therein lies the problem. Satisfied with the discovery of a mechanistic explanation, we fail to dig deeper, uncovering both theories and facts which almost entirely undermine the above assertion. Simply put, thinking about obesity from a purely mechanistic standpoint is the path of least resistance, reducing the otherwise labyrinthine task of dealing with the purported growing inci-

6 Ibid.

7 Ibid.

8 Fadiman, A. The Spirit Catches You and You Fall Down (New York: Farrar, Straus & Giroux, 1997).

9 Ibid.

10 Fuks, A. “The Military Metaphors of Modern Medicine,” 8th Global Conference: Making Sense of Health, Illness, and Disease, University of Oxford July 3-5, 2009: 5.

11 Leder 1992, 96.

26

12 May, W.F. “Dealing with Catastrophe,” in Dax’s Case: Essays in Medical Ethics and Human Meaning, Lonnie Kliever, ed. (Dallas: Southern Methodist University Press, 1989): 143.

13 Fuks, 2009, 6.

14 Leder 1992, 95.

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dence of overweight Americans to a simple matter of personal accountability—a perspective that Dr. Bruce Link, a professor of epidemiology at Columbia University, believes to “resonat[e] with the value and belief systems of [our] Western culture that emphasize both the ability of the individual to control his or her personal fate and the importance of doing so”15. In other words, such a framing of the overweight problem intrinsically asserts that “if targets for the reduction of overweight and obesity are not reached, then responsibility can be attributed to individuals who do not engage in recommended and ‘responsible’ eating and exercise behavior”16. On top of that, our satisfaction with a basic—and deeply superficial—physiological explanation of corpulence all-but-eliminates any need to question whether the “obesity epidemic” even exists. Granted, there’s no denying the potency of obesity as a risk factor, and attenuating its incidence in the population is a worthy cause, regardless of whether it has become more prevalent.

However, allowing the ostensible soundness of any mechanistic theory of illness to supersede all doubts and competing theories threatens to seriously undermine our ability to improve health, whether in the physician’s office or the policy wonk’s.

In fact, as alluded to above, the effects of the paradigm shift involving the increasingly reductionist focus of medicine has profound implications for how we view—or whether we even consider—the social determinants of health so crucial to influencing health outcomes across demographics. For example, if, in the case of obesity, we accept Gard’s assertion that “a ‘mechanistic’ science of the body, where body weight is understood simply in terms of energy-in and energy-out, may actually be an unhelpful and misleading way of thinking about population levels of overweight and obesity,” then only by truly considering societal risk factors along with their physiological counterparts can we truly understand the nature of the “fat epidemic”—or whether it even exists17. Indeed, there is a significant amount of evidence buttressing the notion that there exists a “strong and pervasive association between social conditions and disease”18.

Becoming fully cognizant of these so-called “soft” factors in patient care transcends the bounds of the clinic—having implications in health policy as well—as evidenced by the story of “Typhoid” Mary Mallon. The first American ever to be identified as a healthy carrier of typhoid fever, Mal-

lon was forcibly quarantined for most of her life after refusing to adopt a lifestyle accommodating the contagious nature of the aforementioned disease19. At first glance, one might contend that Mary’s obstructionist behavior lent credence to the harsh actions of the public officials involved—after all, there’s no debating the fact that Mary, a cook by trade, would probably be responsible for many more deaths to that lethal (and easily-spread) disease by way of culinary contamination, and her refusal to understand that fact—namely, to accept an alternative job as a launderer—justifies the quarantine imposed. However, considering Mary’s social background, upbringing, and overall perspective—the “soft” factors alluded to earlier— paints a very different picture. For example, why should anyone assume that Mary would readily comprehend the concept of a “healthy carrier”?

After all, not only was this a relatively novel epidemiological concept at the time, with minimal schooling, it is impossible to expect someone of Mallon’s background to accede to such an outlandish notion so quickly.

In addition, the desire to save lives and properly contain typhoid fever was hardly the only motivator for New York City Health Department’s targeting of Ms. Mallon—namely, at the time, it was common to believe that many such diseases found their primary origins in the lower class, unhygienic, ethnically-subjugated immigrants of the slums. Given that that she herself was an immigrant—having been born in Northern Ireland and only moving to the United States at the age of 20—it’s not far-fetched to conclude that Mary, understanding these prevalent prejudices, felt targeted not on any physiological basis, but by the unpopular nature of her class and race (without even having to consider the exacerbating effects of gender inequities), justifying her subversion of dictum. Needless to say, had the public officials at the time taken all of this into account—rather than assessing the situation with proximal factors alone—Ms. Mallon may have lived a (relatively) longer and (certainly) happier life. Now, admittedly, to assert that social attitudes are today—almost a century later—just as toxic as in Mary’s time is to border on hyperbole. Yet, such innate divisions in societal understanding, even today, are pervasive (if not as patently public), and sharp public health disparities are (or at least should be) central to the work of health policy officials, guiding their decisions in ways both subtle and otherwise. To deny the importance of understanding this demographic heterogeneity—and the range of social determinants of health that it encompasses—borders, quite frankly, on naivete.

It is important to note, however, that even omitting concerns

15 Link, B.G. & Phelan, J. “Social Conditions as Fundamental Causes of Disease,” Journal of Health & Social Behavior (Extra Issue 1995): 80.

16 Gard, M. & Wright, J. The Obesity Epidemic: Science, Morality, and Ideology (London: Routledge 2005): 10.

17 Gard & Wright, 2005, 11.

18 Link, 1995, 80.

28

19

Leavitt, J.W. Typhoid Mary: Captive to the Public’s Health (Boston: Beacon Press, 1998).

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not directly related to those of the physician reveals fault lines within the seemingly-invulnerable weave of contemporary medical practice. Namely, although, as mentioned previously, the growing presence of the laboratory in modern medicine has revolutionalized acute care (or “bug-zapping,” if you will), “the major disease burden in this new century is chronic illnesses that can be greatly improved but hardly cured,” afflictions as seemingly ubiquitous as “cardiac disease, chronic inflammatory conditions of the joints, connective tissues, lungs and bowels, diabetes mellitus, mental illness and increasingly, malignancy”20. After all, one could, perhaps, posit that acute care has not been significantly impacted by the adoption of the physiological perspective—at least, not directly. On the other hand, the realm of chronic care is one defined by a patient-centered focus—it is the very essence of what such care entails. Thus, “with the growing impact of scientific technologies, reified diseases become known to the clinician (and pathologist) through a series of abstractions increasingly removed from the patient,” progressively debilitating our ability to capably provide effective care for chronic illness21. If our rapid march to physiological omniscience does not bring us any closer to the primary afflictions plaguing our population, then perhaps the efficacy of our increasingly reductionist perspective needs a critical reevalution.

Irrespective of personal views on the matter, then, it is safe to say that the near-ubiquity of mechanistic reductionism in the 21st century clinic has wrought a myriad of mutations across the spectrum of the medical profession. That these changes have done more harm than good, however—or at least enough to offset benefits—is a phenomenon becoming increasingly clear. This is not to presume that the fruits of the laboratory have no place in the consummate clinic; instead, we must acknowledge that allowing our thirst for physiological understanding supplant the human element at the core of the medical mission is, quite frankly, a disservice to Lia Lee and to Dax Cowart and to Mary Mallon— but most importantly, to the primary protagonist in the health care story: the patient. Ultimately, if the intent of the medical practice is to heal, then our march towards mechanistic reduction, as it stands, is fundamentally unsustainable.

20 21

Fuks, 2009, 7 Fuks, 2009, 6

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Works Cited Fadiman, A. The Spirit Catches You and You Fall Down (New York: Farrar, Straus & Giroux, 1997).

Fuks, A. “The Military Metaphors of Modern Medicine,” 8th Global Conference: Making Sense of Health, Illness, and Disease, University of Oxford July 3-5, 2009.

Gard, M. & Wright, J. The Obesity Epidemic: Science, Morality, and Ideology (London: Routledge 2005), pp. 1-15, 37-61.

Leavitt, J.W. Typhoid Mary: Captive to the Public’s Health (Boston: Beacon Press, 1998).

Leder, D. “The Experience of Pain and its Clinical Implications,” in The Ethics of Diagnosis, José Luis Peset and Diego Gracia, eds. (Amsterdam, Neth: Kluwer Academic Publishers 1992): 95-105.

Link, B.G. & Phelan, J. “Social Conditions as Fundamental Causes of Disease,” Journal of Health & Social Behavior (Extra Issue 1995): 80-94.

May, W.F. “Dealing with Catastrophe,” in Dax’s Case: Essays in Medical Ethics and Human Meaning, Lonnie Kliever, ed. (Dallas: Southern Methodist University Press, 1989).

Rosenberg, C.E. Explaining Epidemics: and Other Studies in the History of Medicine (London: Cambridge University Press, 1992)

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Implications of Direct-to-Consumer Testing for Genes Associated with Athleticism Arun Sharma ‘12 Duke University The creation of numerous direct-to-consumer genomics testing companies within the last decade has made the personal identification of the genetic foundations for physical traits, such as athletic ability, accessible and affordable to the common public. Consumers interested in elucidating their unique set of variants for “athleticism genes” need only to purchase DNA testing kits that scan for relevant genetic markers indicating the presence of particular “athleticism gene” alleles. Results from these analyses can inform individuals about their genetic predispositions for excelling at certain physical activities requiring high endurance, speed, or strength. Test results could potentially be utilized to help athletes develop personalized training programs designed to make the most of one’s genetic strengths. Using this gene data, athletes could also identify harmful gene variants increasing susceptibility to conditions that may manifest due to strenuous physical activity. However, the increased frequency of direct-toconsumer testing for “athleticism genes” also presents the possibility of misusing these test results to assist with genetic doping by pinpointing genes that may need to be “improved.” Additionally, by exploiting these genetic tests, parents may prematurely determine a child’s athletic prospects while he or she is young and ultimately, without the consent of the athlete. Before such genetic analyses become commonplace, the benefits and misuses associated with direct-toconsumer genomic testing for “athleticism genes” must be evaluated and official regulation should be considered.

The rise of next-generation genome sequencing technologies has succeeded in making both sequencing and subsequent data analysis more efficient. Rapid improvements in technologies as a result of breakthroughs such as massively parallel DNA sequencing have drastically reduced costs for researchers and consumers who hope to use gene data for their own purposes1. Consequently, the general public now has improved access to genetic tests for a variety of traits. Tests for a number of single DNA base pair variations, or single nucleotide polymorphisms (SNPs), associated with variable phenotypes are currently available and are easily accessible 1 Rogers, Y. H., & Venter, J. C. (2005). “Genomics: Massively parallel sequencing.” Nature, 437(7057), 326-327.

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to the general populace without the consent of physicians. A SNP can be associated with a particular mutant phenotype or increased susceptibility to a condition because of its potential to alter downstream RNA transcription or protein translation via base-pair modification2. Individual SNPs from across the genome can be associated with traits ranging from disease susceptibility to muscle and athletic performance3. Private direct-to-consumer (DTC) genomics companies such as 23andMe offer individuals whole genome SNP-trait correlation analyses for only a few hundred dollars4.

However, as a downside to the improved accessibility of these analyses, the potential exists for consumers to make misinformed conclusions about athletic ability, among other physical traits, from the results of a single test.

Consequently, the scientific and ethical issues surrounding the use of DTC testing for analyzing athletic potential must be evaluated in order to gauge whether the benefits of genetic testing, such as aiding athletes in designing preventive therapies and improved training regimes, outweigh its concerns, namely the possible overuse and misuse of this technology towards misleading consumers and promoting substance abuse.

It is important to emphasize, that currently available SNP analyses do not allow an individual to definitively establish that he or she will exhibit a particular phenotype due to a certain genotypic SNP mutation.

This is in part because external, non-genetic factors play a large part in determining phenotype. Determination of athletic ability is one such situation where environmental influences have a major role in phenotypic expression. For example, elite Olympic athletes spend hundreds of hours in training, honing their bodies in order to achieve success at the highest levels of competition. These competitors may not come from particularly athletic ancestry, but with dedication to their training, they still emerge victorious. Regardless of training’s influence in developing star athletes, alleles exist for supposed “athleticism genes”, such as the well-known ACTN3 gene, that are tested for by DTC companies such as 23andMe in an attempt to establish a genetic basis for certain aspects of athletic prowess5, 6.

ACTN3 was one of the first genes shown to have a connection to athletic 2 Wang, D. G., Fan, J. B., Siao, C. J., Berno, A., Young, P., Sapolsky, R., Ghandour, G., Perkins, N., Winchester, E., Spencer, J., Kruglyak, et al. (1998). “Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome.” Science. 280(5366), 1077-1082.

3 “23andMe: Genetics just got Personal” Retrieved 04/24/2010, from <www.23andme.com>.

4 Ibid.

5 Ibid.

6 Yang, N., MacArthur, D. G., Gulbin, J. P., Hahn, A. G., Beggs, A. H., Easteal, S., & North, K. (2003). “ACTN3 genotype is associated with human elite athletic performance.” American Journal of Human Genetics, 73(3), 627-631.

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ability due to results from studies indicating that the presence of two ACTN3 alleles, 577R and R577X, correspond, respectively, to proficiency in sprinting and speed-based activities versus endurance and strength-based ones7. Similarly, the ACE gene is another “athleticism gene” that is frequently evaluated by DTC tests, and like ACTN3, particular alleles for this gene are associated with enhanced endurance and strength capabilities8.

It is acceptable to utilize these DTC genomic test results retroactively for the purpose of satiating consumer curiosity as to which allele variant an individual has, or perhaps even to the extent of elucidating one piece of the genetic basis for an elite cross-country runner’s abilities, for example. Perhaps in the future, genome-wide sequencing of the unique complement of “athleticism gene” alleles in an athlete’s genome will allow trainers to devise specialized training routines that can take advantage of the athlete’s genetic predispositions. However, ethical questions arise when such genome-wide scans for athleticism alleles are used proactively to allow parents to effectively decide their child’s athletic prospects. This is only one out of a handful of issues that must be addressed when considering direct-to-consumer genome-wide tests for “athleticism genes”. The benefits of DTC sports gene testing, such as the potential for devising individualized training regimens based on genetics, must be thoroughly evaluated against its scientific and ethical concerns, such as the power to give parents unwarranted control over a child’s future, before such testing is allowed to become commonplace among the athletic community.

One of the most promising benefits coupled with direct-to-consumer testing for athleticism genes is the possibility of identifying alleles that differ from athlete to athlete. Genome-wide SNP analyses focusing on these genes can help determine an individual’s athletic predispositions based on the alleles they carry. As a result, athletes can potentially modify their training to match their genetics, making conditioning more effective towards achieving their goals of physical improvement9,10. In one study focused on the aforementioned ACTN3 gene, individuals homozygous for the R577X strength-associated variant showed the greatest gain in muscle

mass following a 12-week arm workout program, which indicates that there is indeed some benefit to specializing training according to one’s genetic “strengths” 11. In a similar study, test subjects with the ACE II gene “endurance” genotype showed greater improvements in long-distance running abilities over a 6 week period than individuals with the alternative ACE DD genotype12. A future goal would be to use whole genome sequencing to identify all of the allelic variation present in a predefined set of genes related to athletic ability, including ACTN3 and ACE. These gene data could then be used to develop specialized training regimens based on genetic predispositions to physical attributes such as endurance or speed.

Although the current costs of whole genome sequencing are preventing this situation from becoming a reality, some scientists are taking the first steps towards achieving this goal by compiling a list of genes whose alleles are associated with differing fitness phenotypes13.

In addition to potential utility in developing highly personalized exercise programs, direct-to-consumer genome-wide tests can have other benefits for athletes. In particular, DTC testing could help prevent sports-related injuries by identifying “risk alleles” before their associated phenotypes can manifest. For example, studies have shown that head trauma brought about by highly physical sports such as boxing can influence the onset of severe neurological disorders, such as Alzheimer’s disease, later in an athlete’s life14. Additionally, homozygosity for a particular gene allele, APO-E4, is associated with an increased probability of developing Alzheimer’s15. Therefore, boxers with long athletic careers who also possess this variant have a higher risk of developing the disease16, 17, 18. Recent studies have verified these concerns, noting that possession of the APO-E4

7 Ibid.

8 Gayagay, G., Yu, B., Hambly, B., Boston, T., Hahn, A., Celermajer, D. S., & Trent, R. J. (1998).

“Elite endurance athletes and the ACE I allele--the role of genes in athletic performance.” Human Genetics, 103(1), 48-50.

9 Sharp, N. C. (2010). “The human genome and sport, including epigenetics, gene doping, and athleticogenomics.” Endocrinology and Metabolism Clinics of North America, 39(1), 201-15.

10 Wackerhage, H., Miah, A., Harris, R. C., Montgomery, H. E., & Williams, A. G. (2009). “Genetic research and testing in sport and exercise science: A review of the issues.” Journal of Sports Sciences, 27(11), 1109-1116.

34

11 Clarkson, P. M., Devaney, J. M., Gordish-Dressman, H., Thompson, P. D., Hubal, M. J., Urso, M., Price, T. B., Angelopoulos, T. J., Gordon, P. M., Moyna, N. M., et al. (2005). “ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women.” Journal of Applied Physiology (Bethesda, Md.: 1985), 99(1), 154-163.

12 Cam, S., Colakoglu, M., Colakoglu, S., Sekuri, C., & Berdeli, A. (2007). “ACE I/D gene polymorphism and aerobic endurance development in response to training in a non-elite female cohort.” The Journal of Sports Medicine and Physical Fitness, 47(2), 234-238.

13 Bray, M. S., Hagberg, J. M., Perusse, L., Rankinen, T., Roth, S. M., Wolfarth, B., & Bouchard, C. (2009). “The human gene map for performance and health-related fitness phenotypes: The 2006-2007 update.” Medicine and Science in Sports and Exercise, 41(1), 35-73.

14 Mayeux, R., Ottman, R., Maestre, G., Ngai, C., Tang, M. X., Ginsberg, H., Chun, M., Tycko, B., & Shelanski, M. (1995). “Synergistic effects of traumatic head injury and apolipoprotein-epsilon 4 in patients with Alzheimer’s disease.” Neurology, 45(3 Pt 1), 555-557.

15 Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993). “Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families.” Science (New York, N.Y.), 261(5123), 921-923.

16 Sharp, 2010.

17 Mayeux, et. al., 1995.

18 Corder, et. al., 1993.

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allele in individuals who have suffered through traumatic brain injury hinders the recovery process and increases the likelihood of developing neurological conditions such as Alzheimer’s19. DTC tests could also allow competitors to quickly identify genetic mutations that provide susceptibility to other serious inherited conditions such as abnormal cardiac hypertrophy, where an enlarged heart fails suddenly during heavy exercise20, 21. Cardiac hypertrophy is of particular relevance here due to the fact that it is the leading cause of sudden, sports-related death in otherwise healthy athletes, and because DTC tests are currently available for determining susceptibility to this condition22. In the future, proactive and comprehensive genomewide screening of “risk alleles” for a wide range of conditions such as the aforementioned ones will give athletes a chance to reevaluate whether or not to engage in strenuous physical activities that could have adverse effects on their health.

Although direct-to-consumer genomics can help compile an athlete’s unique set of allele variants related to physical ability and, consequently, his or her genetic tendencies, misuse of these same genomic technologies and services could lead to ethical problems, particularly along the lines of cheating and substance abuse. The potential exists for competitors to first have their genomes sequenced and annotated with respect to athleticism genes and then to use this information to procure substances that will either augment their physical strengths or reduce their weaknesses through “gene doping”23. The World Anti-Doping Agency (WADA) recognizes gene doping as a method of using external means to modify gene products or, potentially, even enhance genes themselves in order to gain a competitive advantage24. However, some athletes, such as Finnish crosscountry skiing champion Eero Mäntyranta, have “naturally” enhanced genes that give them a competitive edge25. In Mäntyranta’s case, a 1993 study revealed that his entire family held a unique mutation in the EPO receptor gene, causing the body to naturally produce more red blood cells26.

Therefore, this mutation enabled the muscles of affected individuals in his family to have a greater supply of oxygen during exercise, a valuable asset for endurance events27. Genome sequencing or DTC SNP testing would reveal that most endurance athletes do not have such a rare mutation in their cells, and in an effort to gain the same advantage in endurancebased competitions, some have resorted to using substances banned by the WADA28. Repoxygen, an experimental drug used to raise red blood cell counts in anemic patients, utilizes a viral vector to directly insert an EPO transgene into the body to force the increased production of red blood cells and has already been involved in doping scandals in Europe29, 30. Additionally, because gene therapy via viral transgenic modification is in its infancy, athletes and doctors hoping to perform such procedures must exercise extreme caution. Fatal autoimmune reactions to the transgene-carrying vector retroviruses have been observed in clinical trial patients31.

However, because external transgenes have unique molecular signatures distinguishing them from “natural” genes, genome sequencing could potentially be employed to detect numerous gene modifications in athletes using multiple DNA-altering substances such as Repoxygen32. Similarly, because of alterations such as glycosylation differences in the EPO proteins created from the natural versus the introduced EPO gene, proteomic approaches could be utilized to detect this type of gene doping from the structural differences present in products derived from exogenous genes33, 34 . Genomic approaches associated with both DNA and proteins could hypothetically be used to spot differences from the norm caused by banned substances. However, this scenario is particularly troublesome because sequencing could also initially contribute to the doping problem by informing an athlete of genes that need to be “improved” by illegal means.

Other concerns regarding direct-to-consumer genomic testing are more purely ethical in nature. As mentioned earlier, DTC testing for allelic variants suggesting natural proficiency towards athletic activities such as sprinting or endurance events offers competitors the opportunity to focus their training efforts to best suit their genetic predispositions. But to what

19 Zhou, W., Xu, D., Peng, X., Zhang, Q., Jia, J., & Crutcher, K. A. (2008). “Meta-analysis of APO-E4 allele and outcome after traumatic brain injury.” Journal of Neurotrauma, 25(4), 279-290.

20 Wackerhage, et. al., 2009.

21 Arai, M., Matsui, H., & Periasamy, M. (1994). “Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure.” Circulation Research, 74(4), 555-564.

22 Wackerhage, et. al., 2009.

23 Sharp, 2010.

24 “The 2008 Prohibited List: World Anti-Doping Agency’s World Anti-Doping Code” World AntiDoping Agency (WADA). September 22, 2007. <http://www.wada-ama.org/>.

25 Sharp, 2010.

26 de la Chapelle, A., Traskelin, A. L., & Juvonen, E. (1993). “Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis.” Proceedings of the National Academy of Sciences of the United States of America, 90(10), 4495-4499.

36

27 de la Chapelle, Traskelin, & Juvonen, 1993.

28 Sharp, 2010.

29 Ibid.

30 Azzazy, H. M., Mansour, M. M., & Christenson, R. H. (2009). “Gene doping: Of mice and men.” Clinical Biochemistry, 42(6), 435-441.

31 Wilson, J. M. (2009). “Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency.” Molecular Genetics and Metabolism, 96(4), 151-157.

32 Azzazy, Mansour, & Christenson, 2009.

33 Ibid.

34 Sharp, 2010.

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extent should such preemptive testing be allowed, and in particular, should parents subject their children to such tests in order to determine a child’s athletic future? Some direct-to-consumer companies that offer ACTN3 gene tests to identify speed or endurance variants target their products specifically towards children under the age of eight35. Taking childhood testing to the extreme, one can see a future where proactive genome sequencing allows prospective parents to screen embryos and select those with the best compilation of “athleticism gene” alleles36. Another issue is the possibility of coaches conducting retroactive screening using DTC test results as selection criteria for sports teams and essentially employing genetics as a means to choose between two otherwise similar athletes37. Such an action could be considered a form of illegal genetic discrimination in the United States under the 2008 Genetic Information Non-Discrimination Act (GINA)38.

In a sense however, this situation may not be much different from, for example, the National Hockey League’s VO2 Max test administered to measure a prospective hockey player’s oxygen uptake capabilities, one of many non-genetic tests used to evaluate natural athletic talent39. However, in an effort to prevent consumers from using these DTC tests as determinative diagnostic tools for athletics or even medical purposes, the U.S. Food and Drug Administration (FDA) has informed major DTC genomics companies such as 23andMe and Navigenics of its intentions to regulate genetic tests currently offered by these businesses40. In July 2010 statements issued to five major personal genomics companies, the FDA announced that it would be requiring “pre-market clearance” for genetic tests whose results could be employed as medical diagnoses41. These new regulations could potentially limit access to tests for “athleticism genes” due to the fact that some test kits offered by these companies are comprehensive, combining SNP analyses for genes influencing disease susceptibility with those for

other genes such as ACTN342, 43.

DTC genome-wide testing for ”athleticism gene” alleles holds beneficial potential because, by identifying this unique collection of variants in one’s genome, athletes can devise training regiments to match their genetic needs and also discover harmful genetic predispositions that may manifest through strenuous physical activity. Currently offered analyses can reportedly evaluate an athlete’s genome for predispositions to a variety of traits such as susceptibility to Alzheimer’s disease, muscle performance via ACTN3 and ACE testing, tissue durability, lung capacity, ligament and tendon strength, bodily heat management, and many more44, 45, 46, 47, 48 . However, the availability of testing for this wide range of physical traits opens new possibilities for substance abuse through genomics-assisted gene doping and also raises questions about genetic discrimination. As technologies become more affordable, athletes will more frequently use DTC testing for their own means, but they should not be discouraged from utilizing these tests in a safe and acceptable manner. As testing becomes more common, guidelines must be established to regulate DTC genomics in the context of athletics. Individuals purchasing these tests should be thoroughly educated about their risks and intended uses, and perhaps increasing the number of physicians trained in the field of genetic counseling would benefit individuals looking for guidance in this new era of consumer genomics.

However, consumers must ultimately realize that possession of a particular allele for an “athleticism gene” such as ACTN3 cannot be the sole predictive genetic factor for athletic excellence because multiple gene networks contribute to abstract traits such as speed or endurance. Until a perfectly comprehensive genome-wide test for all possible performance-associated genes is developed, indications of future athletic performance based solely on DTC testing should not be viewed as infallible predictions.

35 “Atlas First SportGene® test.” Retrieved 03/01, 2010 from <http://www.atlasgene.com/>.

McNamee, M. J., Muller, A., van Hilvoorde, I., & Holm, S. (2009). “Genetic testing and sports medicine ethics.” Sports Medicine (Auckland, N.Z.), 39(5), 339-344.

36 Wackerhage, et. al., 2009.

37 McNamee, M. J., Muller, A., van Hilvoorde, I., & Holm, S. (2009). “Genetic testing and sports medicine ethics.” Sports Medicine (Auckland, N.Z.), 39(5), 339-344.

38 McNamee, Muller, van Hilvoorde, & Holm, 2009.

39 Vescovi, J. D., Murray, T. M., & Vanheest, J. L. (2006). “Positional performance profiling of elite ice hockey players.” International Journal of Sports Physiology and Performance, 1(2), 84-94.

40 Carmichael, M.C. (2010). “FDA Likely to Require Pre-market Clearance for DTC Personal Genomics Tests”. Newsweek, Retrieved 07/11/2010from <http://www.newsweek.com/blogs/the-humancondition/2010/06/11/breaking-fda-likely-to-require-pre-market-clearance-for-dtc-personal-genomics-tests. html>.

41 Carmichael, 2010.

42 43 44 45 46 47 48

38

Ibid.

“23andMe: Genetics just got Personal”.

Ibid.

Yang, et. al., 2003.

Gayagay, et. al., 1998.

Mayeux, et. al. 1995.

“Athleticode.” Retrieved 09/06/2010, from <www.athleticode.com>

39

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Works Cited “23andMe: Genetics just got Personal” Retrieved 04/24/2010, from <www.23andme.com>.

Arai, M., Matsui, H., & Periasamy, M. (1994). “Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure.” Circulation Research, 74(4), 555-564.

“Athleticode.” Retrieved 09/06/2010, from www.athleticode.com.

“Atlas First SportGene® test.” Retrieved 03/01, 2010 from <http://www. atlasgene.com/>.

Azzazy, H. M., Mansour, M. M., & Christenson, R. H. (2009). “Gene doping: Of mice and men.” Clinical Biochemistry, 42(6), 435-441.

Bray, M. S., Hagberg, J. M., Perusse, L., Rankinen, T., Roth, S. M., Wolfarth, B., & Bouchard, C. (2009). “The human gene map for performance and health-related fitness phenotypes: The 2006-2007 update.” Medicine and Science in Sports and Exercise, 41(1), 35-73.

Cam, S., Colakoglu, M., Colakoglu, S., Sekuri, C., & Berdeli, A. (2007).

“ACE I/D gene polymorphism and aerobic endurance development in response to training in a non-elite female cohort.” The Journal of Sports Medicine and Physical Fitness, 47(2), 234-238.

Carmichael, M.C. (2010). “FDA Likely to Require Pre-market Clearance for DTC Personal Genomics Tests”. Newsweek, Retrieved 07/11/2010 from <http://www.newsweek.com/blogs/the-humancondition/2010/06/11/breaking-fda-likely-to-require-pre-marketclearance-for-dtc-personal-genomics-tests.html>.

Clarkson, P. M., Devaney, J. M., Gordish-Dressman, H., Thompson, P. D., Hubal, M. J., Urso, M., Price, T. B., Angelopoulos, T. J., Gordon, P. M., Moyna, N. M., et al. (2005). “ACTN3 genotype is associated with increases in muscle strength in response to resistance 40

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training in women.” Journal of Applied Physiology (Bethesda, Md.: 1985), 99(1), 154-163.

Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & PericakVance, M. A. (1993). “Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families.” Science (New York, N.Y.), 261(5123), 921-923. de la Chapelle, A., Traskelin, A. L., & Juvonen, E. (1993). “Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis.” Proceedings of the National Academy of Sciences of the United States of America, 90(10), 4495-4499.

Gayagay, G., Yu, B., Hambly, B., Boston, T., Hahn, A., Celermajer, D. S., & Trent, R. J. (1998). “Elite endurance athletes and the ACE I allele--the role of genes in athletic performance.” Human Genetics, 103(1), 48-50.

Mayeux, R., Ottman, R., Maestre, G., Ngai, C., Tang, M. X., Ginsberg, H., Chun, M., Tycko, B., & Shelanski, M. (1995). “Synergistic effects of traumatic head injury and apolipoprotein-epsilon 4 in patients with Alzheimer’s disease.” Neurology, 45(3 Pt 1), 555-557.

McNamee, M. J., Muller, A., van Hilvoorde, I., & Holm, S. (2009). “Genetic testing and sports medicine ethics.” Sports Medicine (Auckland, N.Z.), 39(5), 339-344.

Rogers, Y. H., & Venter, J. C. (2005). “Genomics: Massively parallel sequencing.” Nature, 437(7057), 326-327.

Sharp, N. C. (2010). “The human genome and sport, including epigenetics, gene doping, and athleticogenomics.” Endocrinology and Metabolism Clinics of North America, 39(1), 201-15.

“The 2008 Prohibited List: World Anti-Doping Agency’s World Anti-Doping Code” World Anti-Doping Agency (WADA). September 22, 2007. <http://www.wada-ama.org/>.

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Vescovi, J. D., Murray, T. M., & Vanheest, J. L. (2006). “Positional performance profiling of elite ice hockey players.” International Journal of Sports Physiology and Performance, 1(2), 84-94.

Wang, D. G., Fan, J. B., Siao, C. J., Berno, A., Young, P., Sapolsky, R., Ghandour, G., Perkins, N., Winchester, E., Spencer, J., Kruglyak, et al. (1998). “Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome.” Science. 280(5366), 1077-1082.

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