Volume XI Issue i

Volume XI Issue i Spring 2015

PENN BIOETHICS JOURNAL

Contemplating Human Worth

Stem Cells, Selective Abortion, and A Conversation with Dr. Peter Reese

Penn Bioethics Journal EDITOR-IN-CHIEF Ruchita Pendse MANAGING EDITORS Lucy Chen Stephen Cho Kurt Koehler Darby Marx Samip Sheth Girish Valluru PUBLISHER Lucy Chen TREASURER Timothy Zhou

The Penn Bioethics Journal (PBJ) is the premier peer-reviewed undergraduate bioethics journal. Established in 2004, the Journal provides a venue for undergraduates to make contributions to the field of bioethics. Embracing the interdisciplinarity of bioethics, PBJ reviews and publishes original work addressing debates in medicine, technology, philosophy, public policy, law, theology, and ethics, among other disciplines. The biannual issue also features news briefs summarizing current issues and interviews with eminent figures in the field. Authors and the editorial staff alike have a unique opportunity to experience the peer-review process through the collaborative, rigorous review and preparation of the Journal. With an audience ranging from undergraduates to scholars in the field to the broader public seeking unbiased information, the Penn Bioethics Journal occupies a unique niche in the field of bioethics.

Email bioethicsjournal@gmail.com for more information about bioethics at Penn.

www.bioethicsjournal.com

ASSOCIATE EDITORS John George Armstrong* Heba Arshad Jamie Atienza Sharika Bamezai* Adarsh Battu* Brett Bell Caroline Benson Andrew Bright Josh Bryer Thomas Buckingham Ryan Byun*+ Soomin Cho Alanna Cruz-Bendezu Jessica Davis Carlos Dos Santos Ryan Fan Alys Ferragamo* Claire Fishman* Matt Foman Michael Fortunato Perry Goffner Elizabeth Gonzalez Andy Guo Margaret Hanna+ Brian Hirsh Georgia Huang Edward Jing

Heather Kim Daniel Klyde* Sriharsha Kolla James Lee Jessie Lu* Daniel Lundgren Teodora Maftei Lilian McKinley Jacob Morse* Tiffany Nguyen Jack Norleans Gregory Papaioannou Sagar Patel Susannah Rogers* Joebert Rosal Adi Rosen Gabrielle Schlakman Rachel Shaw* Alex Shazad Shashank Sirivolu Samantha Snyder Naomi Stark Kevin Sun Iulia Tapescu Joyce Tien Rob Warshaw* Maelys Yepes

FACULTY ADVISORS Autumn Fiester, PhD Anne Barnhill, PhD * Copy Editor + Associate Publisher

The Penn Bioethics Journal is published twice a year by the undergraduates at the University of Pennsylvania in Philadelphia, PA. Archived editions of the Journal and information about the submission process can be found on our website: www.bioethicsjournal.com.

Permission must be requested for any kind of copying, such as copying for general distribution, advertising, or promotional purposes, creating new collective works, or for resale. Requests for these permissions or further information should be addressed to team@bioethicsjournal.com.

Copyright Š 2015 Penn Bioethics Journal, all rights reserved.

Philadelphia, PA. ISSN: 2150-5462

Contents

Letter from the Editor Ruchita Pendse Editor-in-Chief

Interview 4

Bioethics in Brief

Dr. Peter Reese, Transplant Nephrologist 12 University of Pennsylvania

Articles

The Measles Outbreak and National Vaccine Policy

5

Ending the Stem Cell Debate: The Impact of iPSCs on Embryological Ethics

Data Security and President Obama’s Precision Medicine Initiative

6

Chase Navellier Stanford University

Scientists Concerned about Modifying Human Embryos

7

Presidential Bioethics Commission Brief: Ethics and Ebola

8

USDA Approves GMO NonBrowning Apple

9

Growing Aborted Fetus Kidneys in Rats for Transplantation Updates to Fall 2014 Briefs

10

11

The Principle of Procreative Beneficence: Objections and Provisions

16

20

Ryan Shean University of Washington

Should We Be Concerned about What Prenatal Diagnosis and Selective Abortion Express?

Ryan LeDuc University of Washington

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Penn Bioethics Journal

Volume XI Issue i

Letter from the Editor

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Dear Readers, Thank you for picking up the 18th issue of the Penn Bioethics Journal (PBJ), entitled “Contemplating Human Worth.” The cover image of this issue depicts the focal point of Michelangelo’s The Creation of Adam, painted in 1512 on the ceiling of the Sistine Chapel in the Vatican. This fresco portrays the Biblical bestowal of humanity to Adam by God, capturing this issue’s titular theme. This cover is particularly appropriate because the fresco’s significant cracking brought on by the passage of time nicely represents how old ideas about human worth have been challenged by technological progress. This tension between advancement and tradition is at the very core of bioethics, and is highlighted in this issue’s contents.

This issue features three essays that pertain to the negotiation of secular definitions of humanity and worth, and that consider how ideas or facets of human worth might constrain action. Our first piece, “Ending the Stem Cell Debate: The Impact of iPSCs on Embryological Ethics,” proposes that the implications of induced pluripotent stem cell technology undermine the idea that human worth can be ascribed to any cell with the potential of becoming human. This realization is argued to clear the path for embryonic stem cell research. The second and third pieces consider how technological developments in pre-implantation and prenatal genetic testing combined with concerns about human worth give rise to new parental obligations. The second piece, “The Principle of Procreative Beneficence: Objections and Provisions,” argues that the obligation to provide the best opportunities to one’s child demands that parents use in-vitro fertilization and pre-implantation genetic screening to select for the “best” possible embryo. The final piece, “Should we be concerned about what prenatal diagnosis and selective abortion express?” takes the opposite stance on the use of screening technology. It condemns selective abortion following prenatal diagnosis of a disability on the grounds that it undermines the worth of members of the disabled community.

This issue also includes PBJ-produced content. The first pages provide briefs on some of the most important developments in bioethics since January 2015. We also sat down with Dr. Peter Reese, a transplant nephrologist at the University of Pennsylvania who chairs the United Network for Organ Sharing (UNOS) Ethics Committee.

The interview inside presents Dr. Reese’s insight into the key issues in transplant allocation, as well his perspective on intersection of ethics and health policy.

Looking inward, April 2015 marked the 10th anniversary of the publication of the first issue of the Penn Bioethics Journal, which was released at the 2005 National Undergraduate Bioethics Conference hosted here at the University of Pennsylvania. This milestone provides an opportunity to recognize the contributions of hundreds of undergraduates over the last ten years who gave part of their time at Penn to PBJ. Their efforts evolved the Journal into what it is today, and helped it to carve a distinct place in the undergraduate bioethics community in this nation and abroad.

A testament to the continued growth of PBJ, this semester we announced a print subscription plan geared toward institutions interested in promoting undergraduate engagement in bioethics. At Penn, undergraduate interest in bioethics has grown so strong that this fall will see the re-launch of the Penn Bioethics Society. The increasing relevance of bioethics calls for future researchers, physicians, lawyers, policymakers, and others to study and engage the field earlier in their academic careers. PBJ is steadfast in its commitment to promote undergraduate exploration of bioethics, and is eager to cover its growing presence.

Here’s to another 10 years of the Penn Bioethics Journal — we hope you will stay with us for the next phase in our journey.

Ruchita Pendse Editor-in-Chief University of Pennsylvania C’16

Bioethics in Brief The Measles Outbreak and National Vaccine Policy

Penn Bioethics Journal Volume XI Issue i

Since January 2015, the United States has experienced such claims have been overwhelmingly proven false by public four major measles outbreaks affecting 178 individuals in 18 health researchers (PublicHealth 2015). Despite opposition, states, the most cases since its documented elimination in legislators are working to tighten California’s vaccine policy in 2000 (“Measles cases” 2015). The most prominent outbreak, order to increase community protection. linked to the popular California amusement park Disneyland, Similarly, lawmakers in Washington and Vermont are is responsible for 73% of these cases. These outbreaks have considering bills that remove either the personal, religious, sparked national discourse about vaccine policy and the role or philosophical vaccination exemptions. Furthermore, of the government in mandating vaccinations.

Oregon’s legislature is considering a bill that, if passed, would In January, Disneyland officials warned that a visitor make it the third state, after Mississippi and West Virginia, to in late December was likely responsible for seven measles solely allow medical exemptions from vaccination (Associated cases throughout California and Utah. The disease was Press 2015). As the state with the highest rate of non-medical most likely contracted overseas (Moulite 2015). Measles vaccine exemptions, some Oregon residents are beginning to symptoms develop one to two weeks after infection and worry about the lack of herd immunity in their community. can initially be mistaken When parents choose for a common cold. not to vaccinate their However, a few days after children, they put not the onset of symptoms, only their children at a characteristic rash of risk of contracting a flat, red spots develops. deadly infectious disease, The disease is highly but also those who are infectious, as 90% of medically unable to unvaccinated individuals receive live virus vaccines who come in contact due to compromised with an infected person immune systems, often contract the disease, from another disease or and approximately 2 in side effects of medical every 1,000 people die treatment (Associated (“Measles” 2015).

Press 2015).

Vaccinations have With the recent uptick long been an essential in diseases that were Source: Centers for Disease Control and Prevention. component of public previously considered health practice, helping eliminated, questions to control the spread of many epidemic diseases. Although about the government’s role in vaccine policy are surfacing the United States lacks a universal vaccination policy, each with new urgency. Despite objections to governmentstate has regulations with which parents must comply so mandated vaccines, the Centers for Disease Control and their children can attend public school. However, many Prevention have stated that more stringent policies are likely states permit medical, religious, philosophical, and personal to develop as a necessity for the protection of national public objections to these policies (Gostin and Hodge 2002). health. (Hinman and Malone 2003).

California is one of 19 states that allows exemption based purely on personal beliefs. Although this policy has existed References since 1961, the rate of parents seeking personal exemptions Associated Press. 2015. “Oregon considers banning most vaccine exemptions.” The Washington Post, February 28. has recently tripled. Currently, 1 in every 40 children in Calefati, J. and L.M. Krieger. 2015. “Measles outbreak: vaccination California is not vaccinated (Calefati and Krieger 2015). exemption would end under proposed California law.” San Jose Mercury Due to the recent measles outbreak, California senators News, February 5. are pushing to eliminate both the personal and religious Centers for Disease Control and Prevention. 2015. “Measles (rubeola).”

February 17. vaccination exemptions. However, governments are wary of Centers for Disease Control and Prevention. 2015. “Measles cases and policing religious objections because, according to University outbreaks.” March 6. of California Hastings College of the Law Professor Dorit Gostin, L.O. and J.G. Hodge. 2002. “School vaccination requirements: historical, social, and legal perspectives.” Public Health Law, February 15.

Rubinstein Reiss, “They do not want to become guardians of Hinman, A.R. and K.M. Malone. 2003. “Vaccination mandates: the public people’s conscience” (quoted in Calefati and Krieger 2015). health imperative and individual rights.” The Centers for Disease Control The strongest opposition to these efforts comes from the and Prevention. so-called “anti-vax” movement, predominantly comprised of Moulite, M. 2015. “Timeline of Disneyland measles outbreak.” NBC Los Angeles, February 4. parents who believe their children developed autism, allergies, PublicHealth.

2015. “Vaccine myths debunked.” or other chronic diseases as a result of a vaccine. However,

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Bioethics in Brief

In the 2015 State of the Union Address, President Barack Obama officially announced the Precision Medicine Initiative, dedicating $250 million to the creation of a national biobank (Handelsman 2015). Based on the National Research Council’s comprehensive report on precision medicine, Obama’s initiative aims to utilize extensive patient information to generate a comprehensive database (Office of the Press Secretary 2015).

Although there are many supporters of precision medicine, this announcement has ignited a controversial debate over the privacy and health equity consequences of personal data that will be shared amongst public health, biomedical research, and healthcare delivery communities (National Academies Press 2011; Klugman 2015).

Precision medicine has been growing in popularity among health professionals because specialization of individual treatments allows for increased efficacy (Klugman 2015).

Rather than general diagnoses based on correlations between symptoms and diseases, precision medicine aims to create highly customized treatment plans based on the patient’s genetic information while also incorporating exogenous factors such as physical activity, lifestyle, behavior, physical environment, and socioeconomic status (Kaiser 2015; National Research Council 2011). Developing and improving this treatment approach relies on sharing information across health disciplines about the relationship between different genetic markers and treatment responses, especially for cancer (Office of the Press Secretary 2015).

The collection of such a vast amount of data is accompanied by the obvious inherent risk of data breaches and serves as the basis for a $5 million investment allocated to the Office of the National Coordinator for Health Information Technology (ONC). The ONC will work to ensure privacy in the exchange of patient data across systems (Office of the Press Secretary 2015). However, scientists have proven that it is possible to link a genomic sequence used in research to the identity of the patient, which implicates a potential severe privacy breach (Gymrek et al. 2013). Even current laws such as the 2008

President Obama introduces the Precision Medicine Initiative January 20 during his 2015 State of the Union Address. He dedicated $250 million to create a national biobank. Source: Reuters.

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Genetic Information Nondiscrimination Act cannot protect individuals from discrimination and privacy invasion by life insurance, disability insurance, or long-term care insurance companies (Rothstein 2009). In response to this criticism, the Obama Administration recognized the need to address and develop a legal framework to protect participants (Office of the Press Secretary 2015). Despite these efforts, the risk of breaches in data security is inherent to data storage and unlikely to ever be completely resolved.

The issue regarding health equity arises from the worry that certain therapies will only be available to individuals with more expensive and comprehensive insurance plans or those who can cover the cost out-of-pocket (Klugman 2015). A key component of this initiative involves forging new publicprivate partnerships to contribute data. Professionals such as David Ledbetter, the Chief Scientific Officer at Geisinger Health System, have expressed a willingness to possibly aid this effort through recruitment of customers (Reardon 2015).

At this stage, it is difficult to determine whether private companies, such as pharmaceutical companies, will use this comprehensive database and continue to charge extremely high prices for more specialized treatments (Kroll 2015).

This would leave poorer individuals without a chance to take advantage of the medical progress that their data may have been used to create in the first place.

In order to move forward with this initiative, it is imperative that laws be established to protect the rights of individuals who agree to share extremely personal information, ranging from the microbial content of their organs to their genomic sequence (National Research Council 2011). Furthermore, policy deliberations should ensure the accessibility of future personalized treatments for all sick patients. Like the development of genetic ethics in response to the Human Genome Project, it is probable that a new subfield of bioethics will develop from forthcoming questions regarding precision medicine (Klugman 2015).

References

Penn Bioethics Journal

Volume XI Issue i

Data Security and President Obama’s Precision Medicine Initiative

Gymrek, M., A.L. McGuire, D. Golan, E. Halperin, and Y. Erlich. 2013.

“Identifying personal genomes by surname inference.” Science, January 18.

Handelsman, J. 2015. “Precision medicine: improving health and treating disease.” The White House, January 21.

Kaiser, J. 2015. “Obama precision medicine plan would create huge U.S. genetic biobank.” Science, January 29.

Klugman, C. 2015. “Precise medicine has imprecise ethics.” Bioethics.net, February 19.

Kroll, D. 2015. “Obama’s precision medicine initiative: paying for precision drugs is the challenge.” Forbes, January 20.

National Research Council Committee on a Framework for Developing a New Taxonomy of Disease. 2011. “Toward precision medicine: building a knowledge network for biomedical research and a new taxonomy of disease.” Washington, D.C.: National Academies Press.

Reardon, S. 2015. “US precision-medicine proposal sparks questions.” Nature, January 22.

Rothstein, M. 2009. “GINA, the ADA, and genetic discrimination in employment.” Journal of Law, Medicine & Ethics, September 28.

Office of the Press Secretary. 2015. “FACT SHEET: President Obama’s Precision Medicine Initiative.” The White House, January 30.

Bioethics in Brief

Scientists Concerned about Modifying Human Embryos In a Nature article published on March 12, Edward Lanphier, for the first time control heredity: genes in the germline that are chairman of the Alliance for Regenerative Medicine, and co- known to play a role in inherited diseases could be corrected by authors called for a halt on the use of technology to modify CRISPR during IVF. human embryos. Such a self-imposed moratorium on research Lanphier and his colleagues (2015), however, warn that these is quite rare and underscores the urgency of the matter. Their germline modifications not only pose serious risks, but also entreaty came in response to an MIT Technology Review article that the purported therapeutic benefits are dubious. Though he claiming that scientists are on the verge of using gene-editing and his fellow authors are all involved in areas of work related techniques to edit embryonic DNA (Regalado 2015). The rumors to editing somatic (non-reproductive) cells with the hope of were confirmed in April by a Protein & Cell paper published by treating illnesses, they believe that embryonic modification researchers at Sun Yat-sen University in China who attempted would have unpredictable and possibly disastrous consequences to modify the gene responsible for β-thalassaemia, a blood for future generations, rendering its use ethically reprehensible. disorder, in human embryos and who raised concerns about the Lanphier et al. (2015) claim that there is no rationale for using technology’s implementation. This debate it against diseases and that this argument raises complex questions about the ethics is merely a “slippery slope toward much Scientists could of designer babies and whether human more unacceptable uses.” Other critics experimentation is a necessary evil for the hold similar views. Hank Greely, a Stanford ultimate goal of human enhancement.

Law professor, agrees that proponents for the first time Editing the human genome is not a “can’t really say what it is good for,” since new concept. Current genetic therapies it is already possible to test the DNA of control heredity. treat certain illnesses by replacing the IVF embryos and pick the healthiest ones defective gene with copies of the properly (as quoted in Regalado 2015). Germline functioning gene. However, a new technique only three years old engineering could lead to a future of “positive eugenics” that is revolutionizing how scientists make changes to genetic material encourages the spread of supposedly superior genes, ushering in at will, and it has been dubbed the “holy grail of genome editing” a dystopia of superhumans and designer babies for those who (Gasiunas and Siksnys 2013). Called CRISPR-Cas9, this system can afford them (Begley 2015). Perhaps most distressingly, it allows for unprecedented precision in altering DNA, even down would make children the subject of experiments, affecting the to the level of a single base (Mali, Esvelt, and Church 2013). unborn before they are able to consent.

The power of this technique has been demonstrated in various Overall, those against the use of CRISPR to modify the capacities in the lab, and the most advanced implementation to human germline feel the process is too nascent to understand its date occurred in China in early 2014 in which twin macaques true ramifications. They argue for a very cautious approach with became the first primates born with CRISPR-edited genomes many more nonhuman trials. To date, a dozen countries have (Rojahn 2014). banned germline engineering. The European Union has even The benefits of the system lie in its simplicity of use and stated that meddling with the gene pool goes against human accuracy of performance. The CRISPR system utilizes a dignity and human rights (Regalado 2015). Time will tell whether mechanism originally discovered in bacteria as an adaptive more scientists follow Lanphier’s counsel as a harbinger or chase immune system analogous to that in humans. In gene editing, human advancement as their destination. scientists employ the bacterially derived Cas9 enzyme and a synthetic guide RNA to introduce a double strand break at any References point specified by the guide RNA along the DNA molecule. The Begley, S. 2015. “Scientists Call for Halt on Experiments Changing DNA of Human Embryos.” Reuters Science, March 12. cell has a system called homology directed repair (HDR) that Cyranoski, D. 2015. “Scientists Sound Alarm over DNA Editing of Human fixes any double-strand DNA lesions by copying the identical Embryos.” Nature News, March 12. base pairing present in the nucleus that was cut out by Cas9. Gasiunas, G. and V. Siksnys. 2013. “RNA-dependent DNA Endonuclease Cas9 of the CRISPR System: Holy Grail of Genome Editing?” Trends in Microbiology, Scientists can exploit this process by providing their own tailor21(11): 562-567. made genetic material, since their template will ultimately be Lanphier, E., F. Urnov, S.E. Haecker, M. Werner, and J. Smolenski. 2015. “Don’t integrated into the cell’s DNA as long as it is present during Edit the Human Germ Line.” Nature, 519(7544): 410–411.

HDR (Timmer 2015). CRISPR has been proven to accurately Liang, P., Y. Xu, X. Zhang, C. Ding, R. Huang, Z. Zhang, J. Lv, X. Xie, Y. Chen, Y. Li, Y. Sun, Y. Bai, S. Zhou, W. Ma, C. Zhou, and J. Huang. 2015. “CRISPR/ target specific points in the mammalian genome (Timmer 2013).

Cas9-mediated gene editing in human tripronuclear zygotes.” Protein & Cell, The CRISPR system also holds different ethical implications 6(5): 363–372. than current gene therapies for editing embryos, in that it could Mali, P., K.M. Esvelt, and G.M. Church. 2013. “Cas9 as a versatile tool for be used in germline cells—the egg and sperm cells—before engineering biology.” Nature Methods 10(10): 957-963. fertilization even occurs. These changes would subsequently be Regalado, A. 2015. “Engineering the Perfect Baby.” MIT Technology Review, March 5. passed on to future generations, creating permanent changes and Rojahn, S.Y. 2014. “Monkeys Modified With Genome Editing.” MIT Technology Review, January 30. possibly eliminating harmful genes from the genome (Cyranoski Timmer, J. 2013. “Bacterial ‘immune system’ used to engineer human DNA in 2015). Those in favor of using the CRISPR process for human human cells.” Ars Technica, January 3. enhancement wholeheartedly believe that these therapeutic Timmer, J. 2015. “New DNA construct can set off a ‘mutagenic chain reaction.”

Ars Technica, March 23. benefits have the potential to reduce suffering. Scientists could

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Bioethics in Brief

Penn Bioethics Journal

Volume XI Issue i

Presidential Bioethics Commission Brief: Ethics and Ebola

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On February 26, 2015, the Presidential Commission for the Study of Bioethical Issues released a brief titled “Ethics and Ebola: Public Health Planning and Response” (Viers 2015). President Barack Obama asked the Commission to produce such a brief in light of the recent outbreak of Ebola in West Africa, which has claimed the lives of more than 10,587 people (Presidential Commission 2015). The Brief seeks to address the numerous ethical challenges raised by Ebola and offer guidance for appropriate interventions.

The Commission, formed in 2009, is comprised of 11 experts of science, ethics, law, and public policy and is chaired

by University of Pennsylvania President Amy Gutmann.

The Commission has previously advised President Obama on issues such as synthetic biology, genome sequencing, and neuroscience research (AZO Network 2015).

In their opening letter for the “Ethics and Ebola” brief, Gutmann and Vice Chair James Wagner state, “The current Ebola epidemic reveals how the response to outbreaks of infectious disease reflects our national values” (Presidential Commission 2015). The Commission used the recent Ebola epidemic to gauge our understanding of public health emergencies, both domestically and internationally, and stressed the importance of public engagement and education to improve preparedness (Zhang 2015). The Brief ’s core is comprised of seven recommendations on how to prepare America for public health emergencies, with a discussion of the ethical relevance of each recommendation.

The seven recommendations can be summarized as : 1. The U.S. has the responsibility to participate in global responses to public health emergencies.

2. The U.S. should improve its domestic and international global health response capabilities.

3. Officials have the responsibility to support public education on global health emergencies.

4. Ethical principles should be included in all public health decisions and qualified public health ethics experts should be readily available.

5. Quarantines and travel should be as least restrictive as possible.

6. Research conducted during the Ebola epidemic should provide all patients with the best available supportive care, and placebo experiments must be properly designed.

7. All bio-specimens must be obtained ethically and with proper patient consent (Presidential Commission 2015).

Source: Presidential Commission for the Study of Bioethical Issues.

In addition, the Commission emphasizes the importance of strengthening all aspects of our public health response and global health infrastructure at large to facilitate or enhance all seven recommendations (Presidential Commission 2015).

The Commission is also concerned about public health issues in developing countries. The use of placebos in developing countries where high quality care is unavailable to patients is an important discussion in the Brief. Patients do not have access to advanced drugs and treatments; thus, a placebo may be the only “treatment” option a patient has, which could lead to prolonged illness or even death. The Commission has deemed the deception of the poor unethical and has set strict regulations on placebo use during public health emergencies (Presidential Commission 2015).

The “Ethics and Ebola” brief will shape the way public health emergencies are dealt with for many years to come.

The tragedy of Ebola helped spur conversation about public health at all levels. The suggestions by the Commision will be considered by President Obama to make changes in the way future epidemics are handled both nationally and internationally.

References

AZO Network. 2015. “Bioethics Commission Makes Recommendations on Preparedness for Public Health Emergencies.” February 28.

Presidential Commission for the Study of Bioethical Issues. 2015. “Ethics and Ebola Public Health Planning and Response.” ETHICS and EBOLA: Public Health Planning and Response, February 26.

Viers, H. 2015. “Bioethics Commission, Chaired by Penn’s Gutmann: Ebola Teaches Health Preparedness Requires Ebola Preparedness.” Penn News, February 26.

Zhang, T. 2015. “Bioethics Commission Makes Recommendations on Research Ethics in Public Health Emergencies.” Blog of the Presidential Commission for the Study of Bioethical Issues, March 12.

Bioethics in Brief

USDA Approves GMO Non-Browning Apple

Volume XI Issue i

turn brown.” Gizmodo, February 14.

Penn Bioethics Journal

On February 13, the US Department of Agriculture scientist at the Center for Food Safety (CFS), suggested that (USDA) cleared the Arctic Apple, a fruit genetically modified “the agency has failed to analyze whether suppressing fruit to be non-browning, for sale to consumers within the next browning with these novel RNA molecules will impact the few years. While genetically modified (GMO) crops have rest of the gene family in the tree” (as quoted in Benson been on the market for about 20 years, most of these genetic 2015). Andrew Kimbrell, executive director of CFS, said that modifications have been focused on improving the efficiency Arctic apples are “completely unnecessary and pose numerous of growing, harvesting, and preserving crops, rather than risks to apple growers, the food industry and consumers” (as improving the aesthetic of the product (Food and Drug quoted in Benson 2015). Wenonah Hauter, executive director Administration 2014). This decision by the USDA marks of Food and Water Watch, added that apple browning is a the first approval of an organism that has been genetically small cosmetic issue that consumers and industry have dealt modified solely for aesthetic purposes, reigniting an old ethics with successfully for generations, and that it is problematic that debate about GMO products, with a new twist.

Arctic apples will not necessarily be distinguished from other Developed by Okanagan Specialty Fruits (OSF) of Canada, sliced apples (Hauter 2015). In addition, Hauter suggested that Arctic Apples are a modern marriage of nature and science the USDA has failed to consider potential impact on U.S. and that utilizes genetic engineering to reduce the expression international markets, as major apple growing associations of the gene that makes normal apples have opposed the fruit because they are turn brown (Zhang 2015). Neal Carter, afraid of consumer distrust (Doering president and founder of OSF, stated 2015). that he is confident that apple growers Though there are potential benefits and consumers will embrace the apples. to introducing a novel approach to food The OSF submitted its petition for production, many are still not prepared its new GMO apple to the USDA in to accept changes in traditional growing 2011, followed by a field test application methods. Consumers remain skeptical in 2012. The modifications in Arctic about the health and economic benefits Apples focus on the enzymatic browning of such modifications. Despite these process, specifically the apple’s level of qualms, the USDA for the first time has the enzyme polyphenol oxidase (PPO). approved the proposal of a GMO fruit When apple flesh is exposed to air, PPO for aesthetic purposes, perhaps setting a mixes with polyphenolics from another precedent for future GMO foods. The part of the apple, catalyzing a reaction first Arctic apples are expected to be that turns white apple flesh brown The Arctic Apple (pictured on right half) is the first USDA approved available in late 2016 (Doering 2015). product for aesthetic purposes. It is a non-browning apple, (Brooks 2012). Through a process GMO compared to a regular apple (left half). Source: Seattle Weekly.

Arctic® Apple is a trademark of Okanagan Specialty Fruits. of gene suppression known as RNA interference, Arctic Apples selectively inhibit the production of PPO, resulting in up to 90% less References Benson, J. 2015. “GMO apples approved despite fierce opposition.” Natural PPO activity than in non-GMO varieties, preserving the more News, March 13. tasteful white flesh (Resnik 2015).

Brooks, J. 2012. “Arctic® Apples help show fruits’ true quality.” Arctic Apples, June 27.

Proponents of Arctic Apples suggest that food service companies would no longer have to treat their sliced apples Charles, D. 2014. “This GMO apple won’t brown. Will that sour the fruit’s image?” National Public Radio, January 8. with antioxidant chemicals like calcium ascorbate to keep them Doering, C. 2015. “USDA approves genetically modified apple that doesn’t looking fresh. Further, Carter believes that the cost savings turn brown.” Great Falls Tribune, February 15. “can be huge … you could make a fresh-cut apple slice 30% Food and Drug Administration. 2014. “Genetically engineered animals.

Consumer Q&A.” September 4. cheaper” (as quoted in Charles 2014). In addition, the USDA Hauter, W. 2015. “USDA approves GMO Arctic Apples despite opposition.” has noted that these “genetically engineered apples are unlikely Eco Watch, February 13. to pose a plant pest risk to agriculture and other plants in the Milkovich, M. 2011. “Non-browning apple cause controversy.” Fruit Growers News, April 29.

United States” (as quoted in Tinker 2015). Through Arctic Apples, the USDA has opened doors for other food industries Resnick, B. 2015. “Would you buy a genetically modified apple that doesn’t go brown?” National Journal, February 20. to take advantage of genetic modification to sell foods.

Tinker, B. 2015. “New frontier in apples: Red or golden but never brown.”

However, the novelty and unfamiliarity of the product CNN, February 16. has also generated skepticism. Doug Gurian-Sherman, senior Zhang, S. 2015. “The U.S. just approved its first GMO apple, which doesn’t

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Bioethics in Brief

Penn Bioethics Journal

Volume XI Issue i

Growing Aborted Fetus Kidneys in Rats for Transplantation

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In January 2015, Ganogen, a biotech company based in California, published an article in the American Journal of Transplantation on the feasibility of growing aborted human fetal kidneys in rats for future use in drug discovery and fetal transplants. While Ganogen has not explicitly stated an interest in using lab grown kidneys for adult transplants, the media has shown much concern for this potential application of Ganogen’s research. Despite the necessity of kidney transplants, especially for neonates and infants, the ethical implications of harvesting kidneys from aborted fetuses demand consideration.

While the concept of growing kidneys in rats is not entirely novel, Ganogen recently developed a device critical to its feasibility. The arterial flow regulator (AFR) device equalizes the arterial pressure and blood flow to the human fetal kidneys from the rats’ circulatory system, which would otherwise have a different blood pressure and flow from the conditions necessary for the fetal kidney (Chang et al. 2015). Researchers tested the success of the AFR innovation by removing rats’ kidneys 30 days after human fetal kidney transplants. The human kidneys’ survival and even modest growth over the subsequent four months established the viability of the AFR technology.

Ganogen researchers hope to perfect the technique such that the fetal kidneys can be grown and matured in the rats, to a stage where they can be used for drug development and possibly be transplanted into fetuses in the womb (Chang et al. 2015). The need for fetal kidney transplants results from developmental renal abnormalities, which is a symptom of over 73 genetic syndromes. These include Di George’s syndrome, a condition caused by a deletion on chromosome 22, which results in either the malformation of kidneys or the failure to develop kidneys all together (Sanna-Cherchi et al. 2007).

Although the media has mentioned adult transplant as a possibility, successful transplant of human fetal kidneys in adults is very far beyond the horizon. The kidneys would have to grow significantly more before they could be used in adults, likely beyond what a rat could sustain.

However, the demand for kidneys in America is high, and there is significant interest in alternative solutions for the shortage of kidneys, besides traditional organ donation.

Ethical concerns have been raised surrounding the technology, as abortion in itself remains a controversial topic. Harvesting fetal tissue from aborted fetuses, despite its benevolent intentions, adds another layer of ethical complexity to the discussion. Arguments against the procedure include those articulated by pro-life advocate Jim Sedlak, who believes it is “totally immoral” and sees it as “another outlandish use of aborted babies to produce results that humans think are good” (as quoted in Zagorski 2015). Moreover, some have raised a fear of fetal abortion

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American society is morally uncomfortable enough about abortion that growing organs from fetal remains will never be accepted. ” - Arthur Caplan

farms, where women are forced into abortions for fetal organs, and of the commercialization of organs more broadly (Adams 2015).

To counter such arguments, Ganogen currently only asks women for the permission to use kidneys after the decision to abort has been made and does not use federal funds for the research (Chang et al. 2015). Eugene Gu, CEO of Ganogen, has suggested additional possible restrictions on the procedure, stating, “the U.S. public may find this technology more palatable if we restrict the organ recipients to only neonatal and fetal patients who have basically no other alternative to save their lives.”

Another potential restriction could involve limiting the source of fetal organs to abortions that were necessary for the health of the mother or those done in cases where the fetus would not survive (Lewis 2015).

These complex ethical and moral objections may limit the potential of growing fetal kidneys in rats even if it is scientifically promising. This sentiment is echoed by New York University bioethicist Arthur Caplan, who writes, “American society is morally uncomfortable enough about abortion that growing organs from fetal remains will never be accepted, and will be banned in state after state” (as quoted in Lewis 2015).

References

Adams, M. 2015. “No longer science fiction: Aborted human fetuses harvested to grow kidney organs in rats for transplantation into human patients.” Natural News, January 26.

Chang, N.K., J. Gu, S. Gu, R.W. Osorio, W. Concepcion, and E. Gu. 2015. “Arterial flow regulator enables transplantation and growth of human fetal kidneys in rats.” American Journal of Transplantation, 15(6): 1692–1700.

Lewis, T. “Growing human kidneys in rats sparks ethical debate.” Live Science, January 21.

Sanna-Cherchi, S., G. Caridi, P.L. Weng, F. Scolari, F. Perfumo, A.G. Gharavi, and G.M. Ghiggeri. 2007. “Genetic approaches to human renal agenesis/hypoplasia and dysplasia.” Pediatric Nephrology, 22(10): 1675-1684.

Zagorski, S. 2015. “Scientists harvest organs from aborted babies to use in animal research.” Life News, March 5.

Updates to Fall 2014 Briefs Update to “Teenager Forced to Undergo Chemotherapy”

Update to “Three-Parent Babies: A Debate of Eugenics” In our Fall 2014 issue, we published a brief on the creation of “three-parent babies,” in which the child’s mitochondrial DNA (mtDNA) is from a second woman who is not the mother. Through the replacement of a mother’s mutated mtDNA with the healthy mtDNA of another woman, this technology has the potential to prevent the inheritance of mitochondrial diseases like muscular dystrophy.

In February 2015, the United Kingdom became the first country to formally approve the use of this technology. The lower House of Commons passed the measure on February 3 by a vote of 382-128, and the House of Lords followed suit on February 24 with a vote of 280-48. Couples in the UK will be allowed to apply for licenses beginning in August 2015 to employ this technology during IVF. It is expected that about 150 babies will be born each year using this technique.

References

References

Briggs, B. 2015. “Judge: Cassandra C. Can’t Go Home Amid Cancer Treatments.” NBC News, April 1.

NBC News. 2015. “Cassandra C, Teen Forced to Undergo Chemo, Is Ready to Head Home.” April 27.

Penn Bioethics Journal. 2015. “Teenager Forced to Undergo Chemotherapy.” January.

Source: The Daily Mail.

Gallagher, J. 2015. “MPs say yes to three-person babies.” BBC Health News, February 3.

Penn Bioethics Journal. 2015. “Three-Parent Babies: A Debate of Eugenics.” January.

The Guardian. 2015. “Britain’s House of Lords approves conception of three-person babies.” February 24.

Sharika Bamezai Alys Ferragamo Claire Fishman

Michael Fortunato Elizabeth Gonzales Andy Guo

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Bioethics in Brief Contributing Writers

Penn Bioethics Journal

In our Fall 2014 issue, we published a brief on the case of a 17-year-old known as Cassandra C., who was refusing to undergo chemotherapy to treat her Hodgkin’s Lymphoma, even though the treatment had an 80 to 85% chance of sending the cancer into remission. Cassandra was a minor, but her mother supported her decision and allowed her to stop going in for chemotherapy, prompting the Connecticut Department of Children and Families (DCF) to file a court case seeking custody of Cassandra to force her to get treatment. In January 2015, the Connecticut State Supreme Court ruled that DCF could take custody of Cassandra and force her to undergo treatment against her will.

Since January, Cassandra has been confined to the Connecticut Children’s Medical Center to receive treatment. She was allowed only a few pre-approved visitors, and her mother was not one of them. In early April, Cassandra petitioned to be allowed to finish her final weeks of chemotherapy by commuting from home, but this request was denied. Finally, in late April 2015, it was announced that her cancer had gone into remission and she would be subsequently discharged.

Now that Cassandra is healthy and back home with her family, it seems this saga has finally come to an end. Though Cassandra may be moving on with her life, this case leaves behind an important precedent in mature minor laws and the power of the state to intervene in medical decisions for minors.

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Interview

A Conversation with Dr. Peter Reese Peter Reese, MD, MSCE is a transplant nephrologist and epidemiologist.

His research focuses on: a) developing effective strategies to increase access to transplantation, b) determining outcomes of health policies on patients with renal disease, and c) testing strategies to improve important health behaviors such as medication adherence. He directs Penn’s Center for Quality, Analytics and Research in Transplantation (PQART). He also chairs the Ethics Committee for the United Network for Organ Sharing (UNOS), which oversees organ allocation and transplant regulation in the United States.

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Penn Bioethics Journal (PBJ): Could you briefly describe your career trajectory, and how you developed an interest in transplant ethics and policy?

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Dr. Peter Reese (PR): I went to medical school mostly because I was very interested in things like social outreach and poverty alleviation. I thought about teaching or social work, but I had a hunger for technical skills. I also liked the idea of medical training because I thought it could increase the impact of my time. It was really only when I encountered transplantation as a trained physician specializing in nephrology that I saw the value of engaging directly in research and policy work. I had initially seen my role in the world as trying to make a difference by helping individual patients one-by-one, and that felt very satisfying.

But transplantation, which is clinically a really fascinating field, immediately presents big dilemmas. These mostly have to do with the scarcity of organs and the fact that the ways to increase the supply are so fraught with ethical pitfalls. It was really when I became a clinician and encountered clinical work that I decided to acquire more skills in research and policy. So I think I got into my career backwards compared to most people. A lot of people who I work with have a life-long fascination with data, analytics, and methods, but I was not one of those people. I think moving organs around different people’s bodies is really cool and it’s that sort of imaginative introduction that made me want to get into analytics and methods.

PBJ: Would you tell us about how you split your time between research, clinical work, and policy work?

PR: I spend about 75 percent of my time doing research and policy development and about 25 percent of my time doing patient care. With the research and policy development work, it’s a bit hard for me to know when I’m doing one or the other.

A lot of the research that I do is geared towards informing policy and making policy proposals. Or, policies are proposed, and I try to anticipate what their effects will be through my research. I also serve as the Chair of the Ethics Committee for the United Network for Organ Sharing (UNOS), and in

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Referring to the National Organ Transplant Act of 1984.

Photo courtesy of Peter Reese.

the past, I’ve been on the Kidney Committee of that same organization. I’ve also been on the Public Policy Committee of the American Society of Transplantation. And serving on those committees is certainly policy work, but it often leads to academic work. For instance, in my current role as Chair of the Ethics Committee, my colleagues and I have been trying to respond to policies that address the question of how to consider the particular needs and ethical duties we have to children when we allocate organs. That work has led me to analyze the effects of allocation policy and based on those findings to go back to policy discussions with new ears.

PBJ: Would you tell us a little more about the UNOS Ethics Committee, the kinds of issues it tackles, and the scope of impact of its deliberations and decisions?

PR: UNOS is a federally funded non-profit that holds the contract to allocate all the solid organs in the US. Back in 1984, Al Gore sponsored a bill1 that was passed by Congress to create the Organ Procurement and Transplantation Network (OPTN), an organized system with transparent allocation rules for organs procured from deceased donors.

An important part of OPTN was that the allocation rules were meant to be pretty transparent; the rules are complicated, but they’re in the public domain. The OPTN contract to handle the actual allocation of organs is held by UNOS. UNOS has a bunch of paid staff, but a lot of the work is done by volunteers like me. So when you want to decide on how kidney allocation is going to work, it’s done by the Kidney Committee, when you want to know how lung allocations work, it’s done by the Lung Committee, and so on by organ. The Ethics Committee doesn’t really generate policy but provides ethics analyses of policies that come out of other committees. So what’s interesting about these committees is that, with the exception of a paid liaison to UNOS, everybody else is a volunteer, including many stakeholders. On some of these committees, including the ethics committee, there are prior living donors, members of the clergy, social workers, professional ethicists, scientists, health professionals, and employees of organ procurement

A Conversation with Dr. Peter Reese organizations like Gift of Life in Philadelphia. So while there are certainly physicians on the committees, they are really just one voice among many. So it’s really interesting work, and it takes a lot of time.

UNOS has been criticized for moving slowly, but I think it’s partially because the committees have this broad range of stakeholders, and it can take time to get everyone to reach consensus. So policies are proposed and developed, and then UNOS goes to every region for these regional meetings, where they present the policies and put them up for vote. For the policies to be implemented, the regions basically have to be in unanimous support of it, so a lot of policies get shot down and then ultimately go to the board.

PBJ: You’ve done some research on finding factors, specifically functional status, that predict the expected utility or longevity of an organ transplant2. How big a role should such factors play in determining who receives a transplant?

PR: The basic tension in the allocation of virtually all scarce healthcare resources is between efficiency and justice or fairness.

It’s always a negotiation between these two principles and that’s definitely the case for kidneys. I studied functional status because when balancing these principles, we definitely believe we need to identify which candidates will benefit the most. It’s not the only thing to take into account, but we know it must be considered. At the extreme, everyone agrees that you would probably never give a kidney to someone knowing they were going to live a month or to someone with a terminal disease such as untreatable cancer. But the tools to forecast survival after

transplant are really limited. I think functional status3, and some related concepts like frailty4, may have some value in helping us forecast survival more accurately. In the studies I’ve been doing, we learned that functional status has a relatively small ability to improve prediction of survival. It didn’t pan out to be as useful a concept as we thought. For that reason, I think a lot of people are focusing on frailty, and we’ll see if that works better. Basically, we need tools to better predict how long people live after transplant.

If we have those tools, it’s likely that we’ll use them to decrease priority for people with the lowest survival probability.

PBJ: The discussion section of your paper on functional status noted the possibility of trying to improve functional status before transplant. Has that been done, and does that improve odds of success after transplant?

PR: What would be great is if we knew we could take people with poor functional status, or who are frail, and put them through rehabilitation — in this case people might call it “prehabilitation” because it’s before the surgery — to get them into the best possible condition. No one has really tested that strategy, but I think it’s a good one. A couple of concrete steps that we could take even now is to measure the function and frailty of people on the waiting list. For those who have worse function or are more frail, let’s have the physicians see them more often. Maybe instead of seeing them every year or two, let’s see them every six months. Then a great study to do would be to see how people do when they are given referral to nutrition, physical therapy, things like that, to improve their global health status. Then, see whether or not they do better after transplant. The other way that this information could be used is to really consider taking people whose frailty and function keeps getting worse off the waiting list, and they themselves might want that.

Reese, P. et al. 2014. R.D. Bloom, J. Shults, A. Thomasson, A. Mussel, S.E. Rosas, K.L. Johansen, P. Abt, M. Levine, A. Caplan, H. Feldman, and J. Karlawish “Functional Status and Survival After Kidney Transplantation.” Transplantation Journal, 97(2): 189-195.

3 Functional status “has potential advantages as a tool to evaluate and counsel patients about transplantation. Adequate functional status depends on physical fitness, sensory function, and the ability to negotiate the external environment” (Reese et al. 2014, see Footnote 2).

4 Frailty is “a composite construct that incorporated poor self-reported physical functioning, exhaustion/fatigue, low physical activity, and undernutrition” (Painter P., A.L. Stewart, and S. Carey. 1999. “Physical functioning: definitions, measurement, and expectations.” Advances in Renal Replacement Therapy, 6: 110-123).

5 “The Department of Health and Human Services (DHHS) issued the Final Rule in March 2000 to replace local and regional organ allocation systems with one national distribution protocol. This caused much debate among states, especially those that had been successful in their endeavors to increase organ donations” (Duda, L. 2005.

“National Organ Allocation Policy: The Final Rule.” American Medical Association Journal of Ethics, 7(9)).

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Source: Reese et al. 2014, see Footnote 2.

PR: This is definitely a problem. It’s inequitable and probably runs counter to the Final Rule5, which is one of the federal regulations that’s supposed to guide organ allocation. It appears as though this big geographic variation runs counter to the regulatory guidance. I think it’s a product of the zones that are basically historical artifacts, and we have to get rid of them. It’s just totally unfair that if you’re on dialysis in New York City versus Tennessee, your ability to get a kidney might vary greatly, and there’s no real reason for it.

Penn Bioethics Journal

PBJ: It’s been well-established that there is considerable geographic variation in access to deceased donor organ transplants. You’ve looked into whether this holds for pediatric transplant access as well. What are some causes for this variation and what do you think can be done on a policy level to increase equity across the US?

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A Conversation with Dr. Peter Reese To its credit, the leadership at UNOS has recognized African-Americans, who register and donate at lower rates that things need to change. For liver allocation, they’re now than others. That data is not very granular; we’d like to know actively entertaining a proposal that would basically redraw a lot more about these groups that are donating at lower the boundaries of the sharing areas to try to decrease this rates. How does education affect it? How do socio-economic variation. The kidney allocation rules were changed pretty factors affect it? When you only know race, gender, and age, recently so they’re probably not going to go back and change you really don’t know that much about people. My sense is them again soon, but I think there’s a lot of consensus that that targeted interventions would be helpful. we have to change these as well. I can help you understand I think there are several barriers to donating. There is just for a moment why some people get a little intimidated by distrust in the medical system that probably plays a role for the process of changing them. If you look at New York state, ethnic minorities. There is a concern, for instance, that their wait times are years shorter if you live in Upstate New York as loved one won’t get the right care or won’t get as aggressive opposed to if you live in New York City. That’s how strange care if they register as an organ donor. I think that’s unlikely, this situation is. If you were to change the rules tomorrow and it’s possible that you could do an intervention at the and say that we’re going to hospital level where the people allocate all the kidneys across who talk to the families are really The process of asking for trained to answer these concerns.

New York State just according to waiting time, no one in Upstate organ donation is a delicate one. Or maybe, if you’re dealing with New York would get a transplant an African-American or Hispanic ...The average physician is not family, trust could be increased if for years because all those kidneys would start going down the person who talked to them very good at this. to New York City where people were from the same background, have been on the waiting list for or if someone like that could be seven, eight, nine years. So a couple years would have to pass, made available if needed. There’s pretty good data that the in theory, before you reached some kind of equilibrium and process of asking for organ donation is a delicate one. You centers in northern New York could start doing transplants can definitely mess it up if you’re not trained. The average again. So it’s a little daunting, but despite that we have to do physician is not very good at this. The average well-trained it. The situation just can’t stand. person that works at an Organ Procurement Organization6 The novel insight of the paper on pediatric access was is probably much more sophisticated at it. Ideally, the person that there are also big geographic disparities for children. should be attentive to the emotional needs of the afflicted This was previously unclear, and the results surprised us family and address such needs gradually over time. So I think because children are very close to the top of the priority list. interventions like that have the potential to increase organ There may be differences in certain areas about how selective donation rates, particularly among ethnic minorities.

Now I think a very tantalizing question is what’s going transplant nephrologists are. In some areas they may be more willing to keep a kid on dialysis and wait longer until a really on with elderly people? Everything I just mentioned wouldn’t good kidney comes forward, but it does appear that disparities pertain to them. So we wonder whether or not older in kidney transplant access hold even for kids. I think that’s individuals or their surrogates perceive that their organs would be as useful. Or, maybe there are certain social mindsets. surprised a lot of people.

Most young people who I talk to are pretty supportive of PBJ: Our last question is about the well-established organ donor registration, and I think for them the thought disparity in deceased organ donation rates among of their own death is very abstract; they aren’t contending different races. What are the main factors for why this with it emotionally right now. For older people, it could be a disparity exists and what would be an example of a more difficult thing to think about. They might not want to think about what would happen if they died, so they might potential intervention? avoid registering as organ donors. But we do need organs for PR: So there’s been a fair amount of research but not a older people, and in fact, transplantation, like many fields ton of successful interventions to increase organ donor of medicine, has a large geriatric element to it. A lot of registration and donation. I guess the first thing I would say is our patients are older, and older organs would serve older that this process happens at two points. People can register as recipients quite well. So I think that’s another very fruitful an organ donor at the DMV or online. But then, if someone area where interventions could be done. is unlucky enough to get a devastating neurological injury and they’re at the ICU, their family is approached to talk Interview by Jacob Morse and Ruchita Pendse. about the decision to donate the organs. We know that there are certain demographic subgroups, like older people and

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“There are 58 organ procurement organizations (OPOs) in the United States. OPOs are responsible for two main functions within their designated service area: 1) increasing the number of registered donors, and 2) coordinating the donation process when actual donors become available.” For more information, see: U.S. Department of Health and Human Services. 2015. “Organ Procurement Organizations.” U.S. Government Information on Organ and Tissue Donation and Transplantation.

Master of Bioethics

University of Pennsylvania www.med.upenn.edu/mbe

Article

Ending the Stem Cell Debate:

The Impact of iPSCs on Embryological Ethics Chase Navellier* Modern science has failed to establish a point in early human development that denotes the onset of traditional rights. As a result, the controversy over the usage of human embryonic stem cells in scientific research has proven to be a difficult topic to address. Those who argue against research frequently point to an embryo’s potential to become a human being; they show that the potential necessitates an embryo be treated as a human in its own right. This paper looks at that argument through the lens of induced pluripotential stem cell (iPSC) technology that enables the creation of stem cells through nuclear reprogramming of adult, differentiated somatic cells. In light of their recent success, iPSCs are now being considered as a way to bypass the controversy by replacing the need for traditionally obtained embryonic stem cells. This paper argues that iPSCs are in fact the key to ending the ethical debate about stem cell research, but through a completely different mechanism. Because iPSC technology can create a viable human embryo, the potential-to-become-human argument must be applied to all somatic cells in order to maintain intellectual consistency. This would have unreasonable implications, namely that human rights must extend to all individual cells in the human body. This conclusion invalidates the potentiality argument, thereby eliminating the strongest secular argument against embryonic stem cell research.

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The Importance of Stem Cell Research

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Is a cell a person? Is a person more than the trillions of cells that constitute his or her existence? As living organisms, we are at our essence an extraordinary chain of chemical reactions and electrical impulses. Yet the term “extraordinary” should not be taken lightly. The spontaneous chemical order that comprises our biology far surpasses anything mankind has been able to construct or comprehend throughout history.

And as a result, at some point between the simplest chemical reactions in our cytoplasm to the emotions shared between two lovers arises something that can only be described as humanity. Where that point exists, however, is the subject of an ongoing debate — a debate that is relevant to the modern world because of its implications for promising new avenues of scientific and technological advancement, among which is the use of embryonic stem cells (ESCs) in medical research.

In the scientific community, stem cells have shown much promise in finding cures and improving biomedical knowledge.

Because these cells have not yet differentiated, they hold a unique status in the biological world of pluripotentiality with the ability to develop into any type of somatic cell. This biochemical property has enabled research groups to make unprecedented progress in developing cures for cancer, diabetes, and neurodegenerative disorders, among many other diseases (Reya 2001; Pagliuca 2014; Parish 2006; Baig 2014).

Moreover, existing contributions only begin to tap into the potential of ESCs, as the molecular processes that govern their

subsequent changes into any and all cell types have almost ubiquitous biological relevance. However, since the first successful culturing of human ESCs in 1998, there has been bitter contention in the United States regarding their use in scientific research. Groups positioned against ESC usage have successfully slowed the pace of research by lobbying for the creation of various legislative policy restrictions for scientists who seek to use stem cells (Robertson 2010). Despite the large-scale controversy, most of the arguments made against stem cell research simplify to a single maxim: entities with the potential to become human beings must be invariably treated as human in their own right. Due to the abstract nature of this claim, refuting such anti-research arguments has proven difficult over the past several years. As a result, relatively little progress has been made in establishing the moral status of an embryo. Recent advances in biotechnology, however, may be the key to ending this bitter ideological war.

Through nuclear reprogramming, cells in adult organisms can now be converted to a pluripotential state only previously associated with ESCs. These artificial stem cells are collectively referred to as induced pluripotential stem cells (iPSCs) and hold great promise in better defining the blurred line between developmental biology and humanity. This paper will argue that the relatively new ability to create stem cells from differentiated adult cells not only represents a massive leap forward in biotechnology, but also an advancement that fundamentally changes the perception of humanity in a

* Chase Navellier is a freshman at Stanford University studying Chemical Engineering and Computer Science. He can be reached at chasen@stanford.edu. Dr. Trisha Stan, Fellow in the Program in Writing and Rhetoric at Stanford University, served as the faculty sponsor for this article.

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Ending the Stem Cell Debate single cell. As a result, this technology will prove to be a game changer in the current ethical debate by allowing us to derail the arguments opposing stem cell research.

The Argument Against ESCs: Human Potentiality

iPSC Technology and the Potentiality Argument

reprogramming of somatic cells is “motivated by the desire to find an escape hatch for obtaining embryonic-like stem cells without destroying embryos.”

As a result, the most significant outcome of the advancement in iPSC technology may not be the replacement of ESCs, but instead the “clarification of the ontological status of all forms of early cellular development along the continuum of natural potentiality that can result in the formation of a fetus.” In other words, by applying intellectual consistency to all entities with the capability to form a fetus, iPSC development fundamentally changes the way that human cells must be treated, for the same distinction placed upon ESCs must be applied to all cells in the human body. As a result, unless that distinction is altered, actions as innocuous as scratching off live skin cells, taking cheek swabs for DNA sampling, pricking fingers to test blood sugar, biopsying live tissue, or compromising any living human cell whatsoever would be immoral. Such a conclusion is indeed unreasonable.

Totipotency Versus Potentiality in iPSCs Of course, it is important to analyze the criticism surrounding such a novel argument. For example, in 2009, University of Utah Neurobiology Professor, Maureen Condic, Franciscan University of Steubenville Professor of Philosophy, Patrick Lee, and Robert George challenge the scientific logic behind the conclusions drawn by Magill and Neaves. The authors begin by injecting doubt about the ability to form human embryos from iPSCs. Following this initial premise, they question whether scientists will actually be able to take iPSCs a step further and create totipotential cells from somatic cells. “Totipotential” denotes cells that can differentiate into any type of body cell. The difference between totipotential and pluripotential cells lies in the ability to form extra embryonic membranes of the placenta. The authors assert that these totipotential cells are the hallmark of embryonic development, and without them and the organic placenta they ultimately form, the argument that iPSCs have the same potential as traditional embryos falls apart.

However, this particular analysis begins to break down for a number of reasons, one of which is the speculation that modern science will be unable to form a viable embryo from iPSCs. Overwhelming consensus within the scientific community shows that the requisite knowledge to form a human embryo from somatic cells is very close at hand. As long

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The nuclear reprogramming that results in iPSCs is often considered a solution for stem cell researchers since it doesn’t require the ESCs that usually result in protest. This outlook is one of shortsightedness, however, because it fails to look at the issue on a deeper level. A Kennedy Institute of Ethics Journal paper (Magill and Neaves 2009) contends that the pluripotentiality seen in iPSCs doesn’t necessarily eliminate the need for ESCs in research. It discusses the theme of trying to replace ESCs with iPSCs and states that such a claim is “premised on a mistaken assumption that iPS cells [are] unrelated to embryogenesis.” With this in mind, the authors argue that the “misplaced belief ” regarding the

Source: The Curious Neuron.

Penn Bioethics Journal

Although many scholars who oppose ESC research are motivated by religious principles, the matter transcends theology and deals with a fundamental right to life. So far there has been no shortage of literature published in defense of the anti-research viewpoint, most of which relies on the same argument. As an example of prevalent secular rhetoric, Robert George, a Professor of Jurisprudence at Princeton University, and Patrick Lee, a Professor of Bioethics at the Franciscan University of Steubenville, claim that any entity with the potential to become a human being must be treated as a human in its own right. The authors point out that, although all human cells share key attributes like the genome, a fundamental distinction between stem cells and somatic cells is the ability to become a new organism. In seeking to establish the difference between embryos and other cells, they call upon the point of potentiality, saying any “type of ‘potentiality’ possessed by somatic cells differs profoundly from the potentiality of the embryo” (George and Lee 2009, 302).

George and Lee (2009) build their argument around the premise that a human being can only arise from ESCs. Their approach is common among scientific-based arguments against stem-cell research and is seen throughout the book Embryo: A Defense of Human Life (2008), co-authored by George with Christian Tollefsen, professor of philosophy at the University of South Carolina. This book focuses solely on scientific (rather than religious or spiritual) arguments in order to conclude that humanity begins at conception. The fundamental premise is that the innate ability to become a person makes an embryo a human being. The authors George and Tollefsen declare that the embryo has all the “structures necessary for providing the new individual with a suitable environment and adequate nutrition,” and that it can “get itself to the uterus,” “burrow” into the uterine wall, and begin “taking in nourishment” from “a congenial environment.” In stating this, they attempt to establish autonomy of the embryo that is synonymous with that of an independent person.

While their conjecture obviously has the fundamental flaw of ignoring the maternal support necessary for all embryological development, it hinges on the premise that embryos are unique through their capability to develop into an adult organism.

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Ending the Stem Cell Debate as seven years ago, scientists already achieved the successful growth of adult mice from iPSCs (Wernig et al. 2007). This of course begs the question as to what is preventing a similar ability in human cells; as of now, no such objection has been raised. Furthermore, the other primary argument posed by Magill and Neaves is that stem cells (embryonic or induced pluripotential) require a placental support system to mature into an organism, whereas an embryo can create its own placental trophoblast. However, Assistant Professor at Ghent University Katrien Devolder (2009) challenges the importance of this fact and openly disparages their argument:

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Although this observation is true, it is not clear why it is morally relevant. A blastocyst consists of two distinct cell types including the inner cell mass (ICM) cells, which eventually become a human being from the embryo proper, and trophoblast cells, which contribute to the placental support system. Although the trophoblast is essential for the further development of the embryo, it does not become part of the full-grown organism. Arguably, it is the ICM cells that are of moral significance, as the trophoblast merely provides the appropriate environment for these cells to develop into the embryo.

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Devolder then considers a hypothetical situation in which a couple undergoes in vitro fertilization and can produce a viable zygote, but not the trophoblast support cells. If the trophoblast is artificially created, there is then no distinguishable difference between a fetus that develops in IVF and a fetus that would develop from a zygote formed from iPSCs (2009). Indeed, this is an important connection to recognize because it seems absurd that anyone could argue that the legitimacy of a human is decreased solely because they develop within a non-natural environment. Considering that distinction between natural and artificial placental support systems was stressed heavily in the argument against equating ESCs and iPSCs, when put in perspective, the premise against applying intellectual consistency to embryonic and induced stem cells further unravels.

At this time, a common point of refutation would be the role of determinism in embryological development. One might claim that the arguments constructed thus far fail to account for whether or not a cell is already destined to develop into a human being. This implies that not only is a cell’s potential to become human a key factor in the bioethical debate, but also whether or not it will become a human if left to its own devices. Obviously iPSCs require a significant amount of manipulation to transform from their original differentiated state, and even more human intervention is then required to create a viable embryo. The argument can therefore be made that although iPSCs may have the same capability as other naturally occurring cells, they still cannot be equated since iPSCs require initial human intervention.

The flaw in this logic, however, is the assumption that any human embryo can develop without human intervention.

For example, the ESCs that have traditionally been criticized are usually obtained from leftover embryos from in vitro fertilization. These embryos have no ability to develop unless

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To say that iPSCs are different because they require human manipulation completely ignores what else goes into allowing embryological development to occur. ” artificially placed inside of a womb. Even then, every embryo relies on a mother for many months. As previously discussed, the role that artificial placentas and humans play in helping to develop a fetus are largely immaterial. All human beings require extended intervention on behalf of their initial development.

To say that iPSCs are different because they require human manipulation completely ignores what else goes into allowing embryological development to occur.

Are ESCs and iPSCs Equivalent?

Transitioning back to the core discussion about equating the potentiality of ESCs and iPSCs, it should also be addressed that discrepancies between the two types of cells still exist.

Since the critique of Magill and Neaves focuses heavily on the current biological differences between iPSCs and ESCs, the overall attitude of scientists regarding the future of iPSC development is highly applicable to the debate. In fact, it is not difficult to see that the overwhelming majority opinion of the scientific community believes in the ability to form viable embryos from iPSCs (since it was done in mice). There is also considerable faith that in the near future ESCs will be able to be replaced altogether with iPSCs for research purposes.

One of many instances of this faith in iPSC technology is a dissertation that discusses the implications of nuclear reprogramming on the treatment of brain disease (Heine et al.

2012). It looks at iPSCs as an incredibly promising technology and an eventual complete replacement for their embryonic counterparts. The authors give credit to the continuing development of nuclear reprogramming technology: “It can be expected that many of the current limitations will be dealt with in the future, just as previous issues have been addressed.”

They display considerable faith in the future development of iPSCs, and in the conclusion segment of their work, they even go on to list the in vivo potential of the cells as a significant and very real area of inquiry. Considering that their work primarily concerns tissue re-engineering for use in applications like treating disease, the fact that they feel the need to mention the in vivo potential of iPSCs is a striking counterargument to Condic et al. Indeed, for all ethical intents and purposes, ESCs and iPSCs must be treated the same.

However, the current differences between ESCs and iPSCs are still very relevant in a research context. While both types of cells can develop into adult organisms, iPSCs will not be able to replace ESCs anytime soon. The authors note the unprecedented success of the field and display considerable faith in its near future, but they also discuss the current

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Ending the Stem Cell Debate biological knowledge surrounding iPSCs and explain that many limitations still exist in the present day, noting that the field presently suffers “from limited efficiency, safety risks, and lack of clear criteria for determining the success of cell reprogramming” (Heine et al. 2012). Specifically, the low success rate in part arises from the fact that the four transcription factors used to create iPSCs often fail to erase all the features of the differentiated cell state. In addition, iPSCs often accumulate transcription errors and chromatin marks that are unrelated to the cell of origin (Bilic and Belmonte 2012). This is neither disappointing nor surprising, for any novel field is almost guaranteed rife with issues at its onset.

But this reality illustrates why ESCs are still very much relevant and very needed in modern biomedical research. To say that we can now disregard ESCs because of the successes that iPSCs have already had is simply false. ESCs are still relevant and controversial.

Implications of iPSC Technology on the Potentiality Argument

References

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Baig, A. 2014. “Cloned microglias with novel delivery system in multiple sclerosis.” Stem Cell Research and Therapy, 4(11): 252.

Bilic, J. and J.C.I. Belmonte. 2012. “Concise review: induced pluripotential stem cells versus embryonic stem cells: close enough or yet too far apart?” Stem Cells, 30(1): 33-41.

Condic, M., P. Lee, and R. George. 2009. “Ontological and ethical implications of direct nuclear reprogramming: response to Magill and Neaves.” Kennedy Institute of Ethics Journal, 19(1): 33-40.

Devolder, K. 2009. “To be, or not to be?” EMBO Reports, 10(12): 1285-1287.

George, R. and C. Tollefsen. 2008. Embryo: A defense of human life. New York: Doubleday.

George, R. and P. Lee. 2009. “Embryonic human persons. Talking point on morality and human embryo research.” EMBO Reports, 10(4): 301-306.

Heine, V., S. Dooves, D. Holmes, and J. Wagner. 2012. Induced pluripotent stem cells in brain diseases understanding the methods, epigenetic basis, and applications for regenerative medicine. Dordrecht: Springer.

Magill, G. and W. Neaves. 2009. “Ontological and ethical implications of direct nuclear reprogramming.” Kennedy Institute of Ethics Journal, 19(1): 23-32.

Paglucia, F., et al. 2014. “Generation of functional human pancreatic beta cells in vitro.” Cell, 159(2): 428-439.

Parish, C. and E. Arenas. 2006. “Stem-cell-based strategies for the treatment of Parkinson’s disease.” Neurodegenerative Dieseases, 4(4): 339-347.

Robertson, J. 2010. “Embryo stem cell research: ten years of controversy.”

Journal of Law, Medicine & Ethics, 38(2): 191-203.

Stier, M. and B. Schoene-Seifert. 2012. “The argument from potentiality in the embryo protection debate: finally ‘depotentialized’?” American Journal of Bioethics, 13(1): 19-27.

Wernig, M., A. Meissner, R. FOreman, T. Brambrink, M. Ku, K. Hochedlinger, B.E. Bernstein, and R. Jaenisch. 2007. “In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state.” Nature, 448(7151): 318-324.

Penn Bioethics Journal

After identical potentiality between ESCs and iPSCs is recognized, the next question is what implications this holds.

In analyzing the effect of iPSCs on the perceived ethics of stem cell research, Katrien Devolder (2009) deduces that “recent advances in iPSC research … present a serious challenge to those who oppose the generation and use of [human] ESCs for research.” Since both forms of stem cells “have an inherent capacity to give rise to adult organisms when placed in an appropriate environment,” Devolder (2009) concludes that they cannot be treated differently in an intellectual setting. Surely as we have seen, the assertion that applying consistency between all entities with the capability to develop into human beings is unavoidable through sound logic. It is from this simple resolution that a corollary with far-reaching consequences must also form. Opponents of stem cell research must either extend their misgivings to all of the trillions of differentiated cells in the human body that can give rise to iPSCs—an avowal that would effectively mean the end of modern medicine—or accept that the potential within an embryo or ESC to become human is no more sacred than the potential to become a human within a somatic or sex cell. Of course, it is certainly possible to construct an argument against stem cell research that doesn’t fixate on the principle of potentiality. However, until a majority of secular dissent regarding stem cell research abandons the potentiality argument, it appears that there is little that can be done to argue against ESC usage without calling upon religious or spiritual reasoning.

As iPSC technology forces us to make the distinction between biology and humanity, long-held viewpoints regarding embryo usage will have to concede. While some people are quick to herald iPSCs as a “solution” to the debate, ESCs are still necessary for use in research while technology continues to progress. More importantly, iPSC replacement should not be considered a solution given the parameters of the arguments that have been made against stem cell research for the last two decades. Rather, iPSCs force the flaws of traditional anti-stem cell issues into the limelight ending much

of the current debate in principle. A University of Münster paper summarizes this sentiment: “[S]cientific insights in the (probably ubiquitous) convertibility of human cells render the notion of intrinsic potentials as the basis of moral status simply obsolete,” (Stier and Schoene-Seifert 2012, 14). Indeed, it seems that in present-day forum there should be little room for continued stem cell debate in a traditional sense given such revelations about nuclear reprogramming. There is of course plenty that can be said using religion or spirituality as justification for further arguments against ESC use, but such conjecture is outside the scope of scientific inquiry.

Moreover, it should be noted that implications of potentiality are not unique to the stem cell debate. Namely, abortion and contraception are two controversies whose arguments also frequently rest on the notion of potentiality.

As the deep-rooted controversy of stem cell debate shows, there is little understanding and consensus about at what point an ongoing chain of organic chemical reactions qualifies as a human being. While it is certainly not a simple question to answer, the outcome of iPSC analysis provides hope that continuing scientific progress will soon be able to better define the spectrum of human development and end other divisive ethical controversies by establishing a clearer understanding of the biology that constitutes our human existence. For now, this incredible iPSC technology can work to remind us that people are far more than the rapidly dividing cells that constitute fetal development. For what makes us human is not a set of self-propagating reactions that have the potential to form another member of our species. Rather, it is a much deeper and emotional condition that transcends any quantifiable characteristic of our chemical makeup— something that a single cell cannot possibly possess.

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Article

The Principle of Procreative Beneficence: Objections and Provisions Ryan Shean*

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With assistive reproductive technologies becoming more and more accessible, many scholars have debated the morality of implementing such technologies. One such scholar, Julian Savulescu, argues for a position known as the principle of procreative beneficence (PPB), which outlines an ethical duty requiring parents to use the aforementioned technologies to select the child who is expected to have the “best” life. This paper will examine this claim in more detail and critique some of the more persuasive arguments against its morality, namely that it can reinforce harmful views towards certain groups and that it has the potential to dramatically exacerbate certain types of inequality. The paper will then argue that while these claims have merit, they cannot outrightly refute Savulescu’s principle, as the moral permissibility of PPB is upheld by the doctrine of double effect, a deontological principle positing that what matters morally are intentions rather than outcomes. In conclusion, some critical provisions are outlined which, if adopted, would provide enough protection from detractors’ worries to merit universal adoption of the principle.

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As biotechnology and assistive reproductive technologies advance to allow greater control over our offspring’s genetic makeup, an examination of the ethical and moral concerns presented by these new technologies is in order. One of the most controversial positions, held by eminent bioethicist Julian Savulescu (2001), is that parents have a moral duty to use these technologies to produce the genetically “best” possible children. In this paper, I will present the argument for the principle of procreative beneficence (PPB) as put forth by Savulescu, as well as the two most convincing objections to this principle: first, that it can express harmful views or preconceptions towards a variety of different groups; and second, that it is overly individualistic and socially irresponsible, with great possibility for exacerbating existing inequalities as well as introducing new ones. After introducing these criticisms of PPB, I will critically reexamine PPB and show that while the objections are wellformed and coherent, they do not present sufficient evidence to completely discount the position advanced by Savulescu and others. Ultimately, I argue that the underlying principle of PPB is sound and that the potential unintended negative consequences of the principle are not intrinsic parts of its intent, making PPB a deontologically ethical duty to be adopted by all.

In order to properly examine the argument, a brief review of the current technologies for assisted reproduction is necessary. Currently, the best and most feasible technique for selecting children with certain traits or genes is a process known as pre-implantation genetic diagnosis (PGD), which when combined with in vitro fertilization (IVF) allows parents to screen a lineup of possible embryos for certain traits and implant whichever one they desire. This is

accomplished by obtaining eggs from the mother, fertilizing them externally, and allowing them to grow for some time.

The eggs are then examined and screened for viability and genetic markers. Any viable embryo can then be implanted and brought to term. This technology will be the focus of this paper. IVF is usually used in response to parental fertility concerns, and PGD is often offered alongside it when the viability of potential embryos is in question. That said, this technology is not offered to parents as a method of selecting for or against traits in children, and is not routinely offered to prospective parents. Some interpretations of PPB dictate that it should be offered to all parents, including those not undergoing IVF. It should not be assumed, however, that this will be the only method of selection or that the arguments herein hold true only for existing technologies. In actuality, these arguments, and indeed this entire discussion, will become far more relevant as these techniques are advanced and refined.

In simplest terms, as put forth by Savulescu, PPB holds that parents have a moral duty to select “the child, of the possible children they could have, who is expected to have the best life ... based on the relevant, available information” (2001, 415). The reasoning behind this claim is supported by what Savulescu (2001) refers to as the “simple case,” which involves two embryos being screened through PGD for implantation.

In this scenario, one embryo has a gene that has been linked to a predisposition to asthma, while the other lacks this gene and thus has no indication of an increased risk of asthma. In setting forth his argument, Savulescu states: “I will understand morality to require us to do what we have most reason to do” (2001, 415). The moral imperative of PPB can be examined through a deontological standpoint.

* Ryan Shean is a freshman at the University of Washington studying Computer Science. He can be reached at ryanshean1@gmail.com.

Dr. Sara Goering, Associate Professor of Philosophy and the Program on Values in Society at the University of Washington, served as the faculty sponsor for this article.

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The Principle of Procreative Beneficence As Michael Parker, professor of bioethics at the This sets forth a very clear and unambiguous imperative to University of Oxford, and many others have pointed out, remove potential dangers for our children, a task which PPB, no real choice between embryos will exist with such a clear if implemented, would complete with ease. Harris furthers difference as in the asthma case, and there will be an almost this position by introducing another thought experiment: overwhelming confluence of genetic markers and indications he asks us to consider a woman who is carrying a fetus that will make selecting the “best” embryo nearly impossible. with a severe disability, who is informed that a procedure This observation, although valid, does not discount the undertaken during pregnancy could remove this disability ethical imperative; it simply points out that performing this completely. Harris states, “It is difficult to imagine how one duty will be difficult. This should be entirely unsurprising, as might defend the actions of a mother who did not treat the moral duties most often are comprised of very complicated illness or disability” (2010, 90). This sets forth an extremely elements, but complexity alone should not preclude or strong philosophical underpinning for PPB, by casting it in a inhibit a concept from being the subject of ethical argument. deontological light as a fundamental part of raising a child.

That said, Savulescu states that in the However, many authors have case of asthma, a single, relatively argued that this policy sends disturbing inconvenient condition, parents messages which could lead to a future have a duty to select the embryo which none but the most staunch Using the principle of in without asthma because, based on of eugenicists should like to live. the information we possess, the child procreative beneficence, all While this is a persuasive case against might be reasonably expected to have parents have a clear duty the PPB, I will address how these a better quality of life. In the words objections fail to seriously undermine of eminent Finnish bioethicist Matti to attempt to provide the the ethical foundation.

Häyry, “Whatever combination of One of the most persuasive best possible life for their things constitutes the worth of an arguments against PPB comes from children. individual’s life as a whole, it is always the disability rights community, better to start one’s existence without which argues that PPB would have traits that can cause problems and with very negative consequences for traits that can turn out to be helpful” already living people who are deemed (2010, 66). This idea of “better” is key to the interpretation “undesirable” and especially for those born in the future, and subsequent defense of PPB. Thus, while asthmatics are when selection has become the norm. The argument states in no way guaranteed to have a reduced quality of life (due that as we continue to strive for perfection, we will become to the myriad of other factors influencing quality of life), as blinded by it and be increasingly less tolerant of diversity or a result of their asthma they certainly can. Therefore, based deviations from our “best” genetic codes: “It seems hard on the available information, the embryo without asthma is for society to accept difference without somehow ranking more likely to have the “best” life. it, thinking of it as inferior, deficient, dysfunctional” (Roth Savulescu argues that once we have accepted the “simple” 1983, 56). While this argument, set forth by William Roth, case and established that parents have a moral imperative to professor of social welfare and public policy at the State select the best embryo, then it follows logically that if couples University of New York at Albany, was not originally brought (or single reproducers in some scenarios) have the means to to bear against the principle of procreative beneficence, it obtain information about their possible children, then they applies very well. Further expanding on this point is Joan have a responsibility to do so. Once they have that information, Rothschild, professor of gender studies at University of they have further responsibility to select the potential child Massachusetts, who asserts that by “transposing the desire with the greatest possibility of the most fulfilling life: the for a ‘normal’ ‘healthy’ child into a dream of a perfect one … “best.” Using PPB, all parents have a clear duty to attempt The rhetoric’s seductive promise widens the gulf between the to provide the best possible life for their children. This duty perfect and the imperfect” (2005, 10). As these technologies applies whenever parents are attempting to reproduce, not become more and more prevalent, those individuals who simply when they are already using IVF. Richard B. Miller, do not use selection, or who possess existing traits being professor of philosophy at Indiana University, corroborates selected against, will be seen as inferior and subsequently be this duty: “Parents’ … duties involve the responsibility to marginalized. assure the welfare of their children” (2003, 30). Given that In response to this, Hastings Center fellow Jonathan PPB is a method of increasing children’s welfare, it should be Glover (2006) stated that the fundamental basis of PPB is universally adopted. that we want our children to flourish, and in attempting to This duty is supported by another prominent bioethicist, ensure our children are free from disabilities, disabled people John Harris, fellow of the Academy of Medical Sciences, are not intrinsically devalued or rendered less deserving who states, “Our obligation not to cause harm to future of respect. Wanting children to flourish is separate from generations has … positive and negative faces. We must not any potential undervaluing of certain groups. It is not an act positively so as to cause harm to those who come after inherent aspect of PPB that disabled people are of lesser us, but we must also not fail to remove dangers which if worth; merely, it would be easier for children to flourish if left in place, will cause harm to future people” (2010, 80). they are initially free from these disabilities. Again, it becomes

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clear that parents have an immutable duty to use all available resources to help their children flourish. At its core, PPB is concerned only with the welfare of the child in question.

It does not intrinsically express negative views or devalue people. Therefore, the idea of PPB as an ethical duty can still be upheld using a principle known as the doctrine of double effect. Originally attributed to Thomas Aquinas, this doctrine holds that negative side effects can be overlooked if they are unintentional and the end goal is positive (Boyle 10). Using this logic, if the foreseen negative consequences could be avoided and we could ensure the best future for our children at the same time, PPB would necessarily be adopted. That said, because the possible harms of PPB are neither necessary nor intended, and parents have a great responsibility to provide good lives for their children, the moral permissibility of PPB can be upheld.

The second argument against the adoption of PPB is that as the current technologies of IVF and PGD are prohibitively expensive and hard to access, procreative beneficence has the possibility of vastly increasing existing inequities. It is for this reason that many bioethicists have expressed their reticence to selective technologies: “If the more privileged among us continue to select out the undesirable ... ‘unacceptable’ children could become clustered increasingly in poorer and marginalized communities” (Rothschild 152). This divide is further explained by George Annas, professor at Boston University, who states, “Ultimately it almost seems inevitable that genetic engineering would move humans into two separable species, the standard issue humans who can then be slaughtered and subjugated by their genetically endowed counterparts” (Rasko 150). While this argument may be exaggerated, the warning is clear. In trying to ensure the best life for our children, we could inadvertently create even more suffering by exacerbating existing inequalities.

However, the opportunity for universal benefits through PPB is very real. While there exists the possibility for furthering inequality, we should not fail to account for eventual universal access to the technology: “We should be slow to assume that a good is too expensive, rare or elitist to be pursued in the hope that eventually it can be made generally available” (Harris 2010, 15). Harris (2010) mentions many technologies, including glasses, antibiotics, and vaccines, now enjoyed by nearly everybody, which started out only in the hands of a privileged few. The existence of any beneficial technology creates possibilities of unequal access; this does not, however, mean that using these technologies is fundamentally immoral. In this case, the doctrine of double effect is particularly compelling, as the intent of PPB is virtuous, and there is a real possibility for removing foreseeable harms. Indeed, the rationale behind PPB envisions a world in which all children flourish.

I have shown that these arguments against PPB, while strong, do not sufficiently attack the foundations or fundamental logic of the principle to discount it. None of the initially persuasive arguments considered here dispute the foundations of PPB; they instead argue that the implementation of it would create enough negative effects to make it immoral to adopt. But PPB does not inherently

engender these negative effects. Thus, both the intentions and the morality of the principle can withstand the toughest of ethical scrutiny.

That said, if we could remove unintended harms, we should. It is clear that the adoption of PPB should be implemented with provisions. First, prospective parents examining these technologies must be fully educated about the risks and benefits of selecting for certain children, as well as the possibility of parental expectations that are not only fallacious but potentially harmful (i.e. that the child will be perfect in every way or behave exactly as the parents hope).

Second, we must ensure that the existing care for and rights of disabled persons are not in any way reduced. In fact, a principle like procreative beneficence, which puts the wellbeing of children at the highest importance, should use the same moral duty to support even better treatment for children who are born with disabilities. Third, a significant body of research and policy must be directed towards making these technologies cheap and equally available, so that they do not exacerbate or serve to perpetuate existing inequalities. Finally, other methods of improving children’s well-being, such as parental education, nutrition, and other forms of prenatal care, should be pursued, because the moral duty which justifies PPB emphasizes the need to give all children the resources to flourish. With these measures in place, the principle of procreative beneficence truly stands up to ethical challenges and should therefore be adopted.

References

Boyle, J.M. 2001. “Toward Understanding the Principle of Double Effect.”

In The Doctrine of Double Effect: Philosophers Debate A Controversial Moral Principle, edited by P.A. Woodward, 7-22. Notre Dame: University of Notre Dame Press.

Douglas, T. and K. Devolder. 2013. “Procreative Altruism: Beyond Individualism in Reproductive Selection.” Journal of Medicine and Philosophy, 38(4): 400-419.

Glover, J. 2006. Choosing Children: Genes, Disability and Design. Oxford: Oxford University Press.

Harris, J. 2010. Enhancing Evolution: The Ethical Case for Making Better People.

Princeton: Princeton University Press.

Häyry, M. 2010. Rationality and the Genetic Challenge: Making People Better?

Cambridge: Cambridge University Press, Volume 11.

Kopelman, L. 2007. “Using the Best Interests Standard to Decide Whether to Test Children for Untreatable, Late-Onset Genetic Diseases.” Journal of Medicine and Philosophy 32(4): 375-394 Miller, R. 2003. Children, Ethics, and Modern Medicine. Bloomington: Indiana University Press.

Parker, M. 2007. “The Best Possible Child.” Journal of Medical Ethics 33(5): 279-283.

Persson, I. and J. Savulescu. 2012. Unfit for the Future: The Need for Moral Enhancements. Oxford: Oxford University Press.

Rasko, J., G. O’Sullivan, and R. Ankeny, eds. 2006. The Ethics of Inheritable Genetic Modification A Dividing Line? Cambridge: Cambridge University Press.

Roth, W. 1983. “Handicap as a Social Construct.” Society 20(3): 56-51.

Rothschild, J. 2005. The Dream of the Perfect Child. Bloomington: Indiana University Press.

Savulescu, J. 2001. “Procreative Beneficence: Why We Should Select the Best Children.” Bioethics, 15(5/6): 413-426.

Saxton, M. 2000. “Why Members of the Disability Rights Community Oppose Prenatal Diagnosis and Selective Abortion” Prenatal Testing and Disability Rights, 147-164.

Article

Should We Be Concerned about What Prenatal Diagnosis and Selective Abortion Express?

Ryan LeDuc* Prenatal diagnostic (PND) testing during the early months of pregnancy are increasingly employed to screen for a range of genetic diseases. A test result indicating the child has a disease associated with disability prompts many parents to consider the termination of the pregnancy. This practice of “selective abortion” and its social implications have generated concern among disability rights advocates. One widely-held view of disability scholars is known as the Expressivist Argument, which claims that selective abortion is harmful and morally problematic because of what it implies about the worth of disabled individuals. This piece presents the debate between disability scholars and bioethicists regarding the Expressivist Argument. In its support, I explore claims that selective abortion after a disability diagnosis implies that there is something “wrong” with the aborted fetus, and that not living is preferable to living a disabled life. In opposition, I consider the impact of disability on the child’s life, as well as positions stating that selective abortion is not inconsistent with supporting the disabled community. Finally, the relationship between disability and identity is explored in the context of this debate. After evaluating multiple viewpoints with regard to the Expressivist Argument, I consider its key takeaways for the future of eugenics debates.

The Expressivist Argument makes the following claim: “Selective abortion after prenatal diagnosis is morally problematic as it expresses negative or discriminatory attitudes, not merely about a disabling trait, but about those who carry it” (Gonter 2004, 2). Imagine the following scenario: a pregnant couple undergoes PND and selectively aborts when a disability is diagnosed. We can conclude that the issue with this particular child, the reason the parents were disinclined to follow through with the pregnancy, was the detected disability. As stated by the well-known bioethicist and pioneer of the Expressivist Argument, Adrienne Asch, “In most cases of … prenatal diagnosis, the woman or couple desires to be pregnant at this time; the termination of the process only occurs because of something learned about this child” (2010, 236).

Through their action, the parents-to-be are devaluing not only the disability alone, but also existing people living with said disability.

Deborah Kaplan, the Executive Director of the World Institute on Disability, states that the message expressed by selective abortion after PND implies, “It is better not to exist than to have a disability” (as quoted in Saxton 2000, 160). The crux of the Expressivist Argument lies in the negative message conveyed by selective abortion that contributes to discriminatory attitudes against people with disabilities.

Asch clarifies what exactly is expressed as a result of PND: selectively aborting a fetus based on the results of PND expresses a harmful message about the disability itself and, more notably, about existing people with that disability (2000). Her views are supported by Dr. Marsha Saxton, principal investigator at the World Institute on Disability and one of the most prominent disability scholars and authorities on the Expressivist Argument.

* Ryan LeDuc is a senior at the University of Washington majoring in Neurobiology and minoring in Psychology and Spanish. He can be reached at leducr@u.washington.edu. Dr. Sara Goering, Associate Professor of Philosophy and the Program on Values in Society at the University of Washington, served as the faculty sponsor for this article.

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The Expressivist Argument

As prenatal diagnostic (PND) technology improves and more disabilities are now identifiable before birth, it is becoming an increasingly common practice for parents to test for potential health problems in a developing fetus. There are various PND tests available, including ultrasound testing and chorionic villus sampling, which are generally performed during the first trimester of gestation, between weeks 8 and 13, and amniocentesis, which is performed early in the second trimester of the pregnancy, typically within weeks 15-19. If the PND test reveals that a fetus is carrying certain markers for a disease or disability, subsequent abortion is a potential course of action. This decision is complicated by the fact that these results can be revealed as late as week 19 (Centre for Genetics Education 2013).

The permissibility of abortion is a separate discussion that falls outside the scope of this paper, as some would argue that abortion is never permissible under any circumstances. Currently, the legality of abortion following PND falls under the jurisdiction of each individual state in the United States, as well as professional self-regulation. In 42 of the 50 states, selective abortion is legal if it occurs before either week 20, week 24, or most commonly, the point of fetal viability — although this varies on a state-by-state basis. While all couples can request to have prenatal diagnostic tests conducted, they are most commonly performed for fetuses at greater risk of having an abnormality, such as those with mothers over the age of 35. Common genetic disorders that can be detected before birth include Cystic Fibrosis, Congenital Adrenal Hyperplasia, Hemophilia A, Duchenne Muscular Dystrophy, Fragile X Syndrome, Sickle Cell Anemia, and TaySachs Disease, among others (Merck Manual 2014).

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Background

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The Expressivist Argument in Prenatal Diagnosis Saxton (2000) points out that discriminatory practices against disabled individuals can contribute to an attitude that is a hindrance when it comes to pursuing a career or becoming an integrated, contributing member in society. Therefore, we need to be careful about what messages the practices like PND and selective abortion convey about this marginalized group.

Saxton and other disability rights advocates argue that the path to reducing selective abortion on the grounds of a disability diagnosis lies in education and awareness: “Simply put, we hope to educate genetics professionals, other medical personnel, and students to consider and learn from the views of the disabled community, and to promote the inclusion of people with disabilities and their families as resources and expert advisers in policy development and clinical services” (Saxton 2000, 161). It is worth noting that disability rights advocates do not recommend an outright ban of abortion; rather, they wish to promote education on the ramifications of such a weighty decision, ensuring that considerable thought has been given and the implications are fully understood.

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Mary Ann Baily, a bioethicist at the Hastings Center, refutes the Expressivist Argument by clarifying the thought process of parents who consider selective abortion, stating, “One can say, ‘She does not want to have a child with Down syndrome,’ and interpret this as a rejection of children with Down syndrome as persons. What I would say is ‘I do not want my child to be born with Down syndrome,’ meaning, ‘If I have a choice, I want the person who will be my child to be born into a body without such potentially significant limitations’” (2000, 66). This small shift in the framing of this decision process undermines the idea that parents who selectively abort a disabled child are devaluing disabled people, and rather proposes that this decision arises from practical considerations.

Another objection to the Expressivist Argument comes from sociologist and disability scholar Tom Shakespeare. He argues that the practice of PND and selective abortion due to disability does not necessarily express a discriminatory attitude towards people with disabilities, stating, “It is not inconsistent to support the rights of existing disabled people, while seeking to prevent more people becoming impaired” (2006, 90). He further explains that a disabled state is not a neutral state and that attempting to reduce the numbers of future disabled people is completely acceptable.

Shakespeare’s logic challenges the conclusion reached in the Expressivist Argument, as he argues PND and selective abortion should not necessarily be viewed as discriminatory or negative practices. While such a negative attitude may be expressed, it is not necessarily expressed.

However, Shakespeare does acknowledge that selective abortion of the disabled can be framed in ways that have negative repercussions for people with disabilities, but he stresses that it is possible to reduce the incidence of disability without devaluing people with disabilities (2000). For example, there is no controversy over the fact that all flour in the United States is fortified with folic acid, which is known to prevent defects in neural tube development that lead to diseases such as spina bifida. Even though the addition of folic acid is done for the purpose of added health benefits,

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The social implications of selectively aborting after a disability diagnosis matter more than the intentions of the action. ”

including the prevention of spina bifida and other birth defects in developing fetuses, it could be argued that this expresses negative sentiments towards those living with spina bifida.

However, Soren Holm (2008), a prominent bioethicist at the University of Manchester, contests Shakespeare’s argument. Holm (2008) claims that whether or not the Expressivist Argument “necessarily” expresses a negative or discriminatory attitude towards people with disabilities is inconsequential. Holm concludes, “Our current practice of prenatal diagnosis and termination of pregnancy therefore to some degree expresses exactly those attitudes that proponents of the Expressivist Objection claim that it does. That the practice does not have to express those attitudes by logical necessity is largely irrelevant to whether it actually expresses them” (2008, 25). Since the reality is that selective abortion is interpreted to devalue people with disabilities, Holm would agree that it is contradictory to support selective abortion while also supporting people with disabilities. Even though there may be no malicious intent in selective abortion, by virtue of the action, it reflects negative views of people with disabilities.

Disability and Identity The Expressivist Argument holds that selective abortion after a disability diagnosis sheds negative light on disabled individuals as whole beings—not just the individual genes that lead to their disability. The Expressivist Argument, therefore, can only be considered a valid argument if the disabled person’s identity is defined by the disability. In an objection to the Expressivist Argument, Baily holds that such an outlook “seems inconsistent with the disability community’s contention that a major part of the unnecessary, socially created burden of a disability is the tendency of people who are not disabled to take a person’s disability and make it the essence of the person, rather than simply one aspect” (2000, 5). If disability is merely one facet of the person and does not define the individual’s identity, then the harms expressed by selective abortion seem much less severe.

Although Saxton agrees with Baily that disability is “not that big of a deal in the totality of your being,” she disagrees with Baily about the implications of this point (2000, 161). Even though the disability is only a small part of the individual, the practice of selective abortion implies that the additional effort required in caring for the disability is not worth it. However large or small of a role the disability plays in the construction of an identity, selective abortion demonstrates that this disability creates enough of a burden to render a life not worth living.

The Expressivist Argument in Prenatal Diagnosis Conclusion In evaluating the moral appropriateness of PND and selective abortion, we must consider the intention of the action, as well as the ultimate outcome and underlying negative messages. In the case of the Expressivist Argument, the social implications of selectively aborting after a disability diagnosis matter more than the intentions of the action. While PND is celebrated as an advancement in biotechnology, the Expressivist Argument makes it clear that we must carefully consider all consequences before acting on the information the technology provides.

PND with selective abortion is just one way that we have increasing control over the characteristics of our offspring. The discussion surrounding the Expressivist Argument is among the first of many forthcoming debates of eugenics. While it is ultimately unlikely that the Expressivist Argument alone will stop the advancements in these technologies, its lasting contribution to the field may be to call attention to the voices of disabled individuals and other marginalized groups in the debates to come.

, MPH/MAB, MSN/MAB, DPT/MAB, M.Div/MAB

References

Asch, A. 2000. “Why I haven’t changed my mind about prenatal diagnosis: Reflections and refinements.” Prenatal Testing and Disability Rights, 236.

Baily, M.A. 2000. “Why I had amniocentesis.” Prenatal Testing and Disability Rights, 64-71.

Gonter, C. 2004. “The expressivist argument, prenatal diagnosis, and selective abortion: An appeal to the social construction of disability.” Macalester Journal of Philosophy, 13(1): 3.

Guttmacher Institute. 2015. “State Policies in Brief: An Overview of Abortion Laws.” March 1.

Holm, S. 2008. “The expressivist objection to prenatal diagnosis: can it be laid to rest?” Journal of Medical Ethics, 34(1): 24-25.

Merck Manual. 2014. “Prenatal Diagnostic Testing.” Detection of Genetic Disorders: Merck Manual Home Edition.

New South Wales Government. 2013. “Prenatal Testing - Overview.” Health Centre for Genetics Education, November 14.

Saxton, M. 2000. “Why members of the disability community oppose prenatal diagnosis and selective abortion.” Prenatal Testing and Disability Rights, 147-164.

Shakespeare, T. 2006. “Questioning prenatal diagnosis.” Disability Rights and Wrongs, 85-102.

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