Volume X Issue ii

Volume X Issue ii

PENN BIOETHICS JOURNAL

Data Interpretation in Health Care

DTC Genetic Testing and Neuroimaging

Also inside:

Conversations with Dr. Steven Joffe and Dr. Matthew Mendlik

Penn Bioethics Journal 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 interdisciplinary nature 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 journal also features news briefs that summarize 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 and rigorous review and preparation of the Journal. With an audience ranging from undergraduates to scholars in the field, PBJ occupies a unique niche in the field of bioethics.

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

www.bioethicsjournal.com

The Penn Bioethics Journal is published twice a year by the undergraduates at the University of Pennsylvania in Philadelphia, PA. All business correspondence, including subscriptions, renewals, and address changes, can be addressed to business@bioethicsjournal.com.

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Copyright Š 2015 Penn Bioethics Journal, all rights reserved.

Philadelphia, PA. ISSN: 2150-5462

Contents EDITOR IN CHIEF Aditi Verma MANAGING EDITORS Evan Cernea Lucy Chen Kurt Koehler Darby Marx Ruchita Pendse Garrett Young PUBLISHER Lucy Chen TREASURER Timothy Zhou ASSOCIATE EDITORS Nikita Agarwal Jackie Andrews John George Armstrong Jamie Atienza Brett Bell Dylan Brown Josh Bryer* Hyung Byun Stephen Cho Alanna Cruz-Bendezu Claire Fishman* Perry Goffner Elizabeth Gonzalez Andy Guo Margaret Hanna*+ Georgia Huang Heather Kim Daniel Klyde* Sriharsha Kolla James Lee Georgio Legerme Teodora Maftei Lili McKinley Gayatri Nangia Tiffany Nguyen Jack Norleans Gregory Papaioannou Sagar Patel Steven Polomski Adi Rosen Danny Sample Gabrielle Schlakman Rachel Shaw Alex Shazad Samip Sheth Shashank Sirivolu Samantha Snyder Kevin Sun Iulia Tapescu Jacqueline Valeri Rob Warshaw Maelys Yepes Ahmed Yousef Samir Zaman Timothy Zhou FACULTY ADVISOR Autumn Fiester, PhD Anne Barnhill, PhD +

* Copy Editor Associate Publisher

Letter from the Editor Bioethics in Brief

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Teenager Forced to Undergo Chemotherapy

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The Halt of Gain-of-Function Research

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Canada to Follow American Footsteps?

Pending Gene Patenting Trial

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Vanguard Consultancies Strengthen Bond between Bioethicists and Scientists

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Three-Parent Babies: A Debate of Eugenics

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NIH Releases New Genome Sharing Policy

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Interviews A Conversation with Dr. Matthew Mendlik

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A Conversation with Dr. Steven Joffe

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Articles Direct-to-Consumer Genetic Testing: An Examination of Privacy and Security Concerns

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Ameay Naravane

Can Recent Neuroimaging Evidence of Consciousness in Vegetative and Minimally Conscious Patients Change our View of Life-Sustaining Treatments?

Joshua Loewenstern

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Letter from the Editor

Aditi Verma Editor in Chief

Penn Bioethics Journal

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Dear Readers,

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In the words of President Amy Gutmann at the 2014 inaugural Bioethics Symposium at Penn, “The sign of an engaged university is its ability to integrate ideas and knowledge across traditional boundaries to confront and address challenging societal questions. This is particularly true in biomedicine, science, and technology, where rapid advances raise particularly complex ethical and policy questions.” Today, the Penn Bioethics Journal serves as a bridge, connecting undergraduates from a variety of backgrounds to bioethics.

We are excited to be at the frontier of bioethics education for undergraduates and, through our publication, allow students to contribute to the field as well.

This issue contains a collection of pieces that cover two issues: genetic testing and neuroimaging. Recent advances in genetics and neuroscience have been influential, but questions still remain as to how to interpret the medical data obtained from these technological advances.

Author Ameay Naravane analyzes privacy and security concerns in the direct-to-consumer (DTC) genetic testing industry, and in his article, he suggests recommendations to better regulate these tests and the data collected with them. A key player in this industry is 23andMe, a DTC genetic testing company that announced on January 6, 2015 a $60 million agreement with Genentech to provide whole genome sequencing data for 3,000 individuals with a genotype connected to Parkinson’s Disease. The individuals have provided explicit permission to 23andMe to share the de-identified genetic information, allowing Genentech access to the largest Parkinson’s disease community data set to date. Naravane evaluates the security and privacy concerns that arise with DTC genetic testing, which has allowed others access to an unprecedented amount of information. He also considers the extent to which individuals providing DNA are informed of and protected from these risks.

Similarly, author Joshua Loewenstern considers the use of current neuroimaging technologies to assist in end-of-life decisions for patients in a persistant vegetative state or a minimally conscious state. In cases such as these, neuroimaging data can be difficult to interpret, potentially compromising the preferences and health of the patient. The extent to which more information can signal recovery, provide hope, and change medical decision-making must be reconsidered in the context of the autonomy the patient maintains and the potential impact on the patient’s family.

The topics chosen by the authors are important, relevant pieces that demonstrate the awareness students have of bioethics issues. Undergraduate education in bioethics provides a starting point for asking difficult questions relevant to medicine, healthcare, and technology. Organizations like the Penn Bioethics Journal allow undergraduates of all career paths to become leaders, well-equipped to grapple with tough problems facing the field. I would like to thank the Penn Bioethics Journal staff, our Managing Editors, Publisher, and Treasurer for their work and dedication this semester. It has been a pleasure serving the journal for the past four years.

Our growth and successes are a testament to the innovation of the Penn Bioethics Journal and the important role undergraduates have in shaping bioethics.

Aditi Verma Engineering and Wharton ’15 University of Pennsylvania

Bioethics in Brief Teenager Forced to Undergo Chemotherapy her lawyers failed to demonstrate that she met the standard of maturity when it comes to her illness and treatment (Berman 2015). Cassandra had also previously expressed concerns to her medical team about upsetting her mother, who is very distrustful of physicians (Briggs 2015), and she had expressed a belief that other natural treatments like vitamins and lifestyle changes have the potential to cure her cancer (Simoni and Buynak 2015, Yang 2015). In light of this, the Court ruled to allow the DCF to continue administering chemotherapy to Cassandra.

Bioethicist Arthur Caplan, founding head of the Division of Bioethics at the NYU Langone Medical Center, agrees with the Court’s decision to support the imposition of chemotherapy.

Given the unusually high probability, 80 to 85%, of treatment success, Caplan writes that “a child would need to have one hell of a reason for not wanting treatment given that this is a type of cancer for which a cure exists.” While strong religious conviction or belief in an alternative medical system could provide more valid grounds for refusal, Cassandra seems to be refusing chemotherapy to avoid the side effects of hair loss, nausea, and fatigue that accompany the treatment, and because she simply does not want to put “toxic poisons” into her body (Caplan 2015).

Cassandra’s legal team is looking to appeal the State Court decision, but most experts are not optimistic about their chances of getting the decision overturned. Despite their support of the court’s ruling, Caplan and others acknowledge that it is still unfortunate and sad that the teen is put in the position of feeling that her body is being violated (Caplan 2015, Harris 2015).

Cassandra writes, “I should have had the right to say no, but I didn’t have that right. I was strapped to a bed by my wrists and ankles and sedated. I woke up in the recovery room with a port surgically placed in my chest. I was outraged and felt completely violated. … This is my life and my body, not DCF’s and not the state’s” (C. C. 2015).

There is some hope that appropriate support and counseling will help to bring Cassandra into agreement with her medical team’s prescribed treatment regimen. Even if it does not, Caplan closes, “Respecting choice is important. Not burying a young teenage girl who would have lived is far more important.”

References

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Berman, M. 2015. “Contemplating youth and the end: Cassandra C. and the ‘mature minor’ debate.” The Washington Post, January 9.

Briggs, B. 2015. “Connecticut teen with curable cancer fights to stop chemo.” NBC News, January 7.

Caplan, A. 2015. “Bioethicist: Why Connecticut teen can’t say no to chemo.” NBC News, January 8.

C. C. 2015. “Saying no to cancer treatment.” The Chicago Tribune, January 12.

Harris, E.A. 2015. “Connecticut teenager with cancer loses court fight to refuse chemotherapy.” The New York Times, January 9.

Nalpathanchil, L. 2015. “Can Connecticut force a teenage girl to undergo chemotherapy?” National Public Radio, January 8.

Simoni, S. and M. Buynak. 2015. “Teen opens up about forced chemotherapy, death.” WTNH Connecticut News 8, January 10.

Yang, S. 2015. “Why a 17-year-old with curable cancer is fighting for the right to refuse chemo.” Business Insider, January 11.

Penn Bioethics Journal

The Connecticut State Supreme Court ruled unanimously on January 8, 2015 that state officials are not violating the rights of a 17-year-old girl by forcing her to undergo chemotherapy against her wishes. The girl, called “Cassandra C.” in court documents (Nalpathanchil 2015), was diagnosed in September with Hodgkin’s lymphoma (Yang 2015), a type of cancer that is curable with appropriate treatment in 80 to 85% of cases (Nalpathanchil 2015). Cassandra’s refusal of care, fully supported by her mother, raises complex ethical and legal questions about whether older minors are capacitated to make fully autonomous decisions, particularly when the stakes are so high.

This decision came after a long saga of missed doctor’s appointments and custody issues. Cassandra’s mother, Jackie Fortin, had a long history of being inconsistent about taking Cassandra to medical appointments, a trend that continued after her daughter’s cancer diagnosis (Briggs 2015). Cassandra’s medical team brought these missed appointments to the attention of the state’s Department of Children and Families (DCF), which decided to take temporary custody of Cassandra in late October 2014 in order to ensure she began receiving treatment in a timely manner. She was released back into the custody of her mother after two weeks on the condition that she began chemotherapy immediately, but after only two days of treatment, Cassandra ran away from home. No one knew where she was for almost a week, but when Cassandra heard that authorities might put her mother in jail on suspicions that Fortin knew where her daughter was hiding, Cassandra came back home. In December, DCF regained custody and hospitalized her at the Connecticut Children’s Medical Center. Since then, Cassandra has been confined to the hospital and is being forced to undergo chemotherapy, being restrained and sedated if necessary (Harris 2015).

The State Court case brought forth by Cassandra’s family against the DCF sought to determine whether Cassandra could be considered a “mature minor,” a legal term for minors who are deemed fit to make autonomous decisions. The family and their lawyers argue that Cassandra is only nine months shy of her eighteenth birthday, after which her competence and authority to refuse treatment would be legally unquestioned. There is some legal precedent supporting the idea that, in the words of Cassandra’s public defender Joshua Michtom, “You don’t go to sleep a 17-year-old knucklehead and wake up an 18-year-old sage” (Briggs 2015).

Dr. Paul S. Appelbaum, director of the Division of Law, Ethics, and Psychiatry at Columbia University College of Physicians & Surgeons, explained to The New York Times that the courts’ key considerations in “mature minor” cases include the seriousness of the medical condition, the child’s maturity, and whether the child’s opinions are being influenced by a parent or third party (Harris 2015). While Connecticut does not currently have explicit “mature minor” doctrines, which 17 states employ to allow some children greater control over their medical decisions, the State Court decision stated that even if such doctrines were presumed to apply in Connecticut, Cassandra and

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Bioethics in Brief

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The Halt of Gain-of-Function Research

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Debates over gain-of-function research have recently surfaced due to controversy over dangerous research and recent laboratory accidents. On October 17, 2014, the White House announced that it would temporarily halt all funding for experiments that seek to study viruses like influenza, SARS, and MERS, as risks were re-evaluated (McNeil 2014).

Gain-of-function research involves scientific experiments that alter pathogens to give them features not presently found in wild type strains. In general, the objective of gain-of-function research on viruses is to provide an understanding of how viruses might mutate in the wild to cause human pandemics, potentially allowing scientists more time develop more effective vaccine strategies (Fidler 2013).

Concerns about gain-of-function research erupted in 2011, when researchers from Erasmus University in the Netherlands and the University of Wisconsin-Madison both claimed independently that they had succeeded in making the lethal H5N1 avian flu easily transmissible between ferrets (Roos 2013). Despite efforts from the National Science Advisory Board for Biosecurity to prevent publishing full details of the studies, two papers were published in May and June 2012. Amid the disputes, a group of 40 prominent flu researchers declared a moratorium in January 2012 of further gain-of-function research that lasted for one year. During this hiatus from research, the Foundation for Vaccine Research (FVR) took the time to study the ethical issues raised by gainof-function studies, the accidental release of lab-generated H5N1 virus, and the risks involved in studying other highly contagious pathogens. Though the FVR seeks to increase funding for vaccine research, the group argues, “Manipulating viruses to make them more deadly than they are in nature is morally and ethically wrong” (Roos 2013).

When the current moratorium, this time imposed by the White House, was announced, executive director of the FVR Peter Hale exalted, “The government has finally seen the light. This is what we [FVR] have all been waiting for and campaigning for.” This time around, the length of the moratorium on gain-of-function research has not been specified, leaving it suspended indefinitely (McNeil 2014).

According to Ian Lipkin, an infectious disease research at Columbia University and member of the FVR, “We are not seeking to shut down all gain-of-function research, but asking that stakeholders meet to establish guidelines for doing it” (Ledford 2013).

Despite approval from the FVR, the moratorium is not welcomed by all parties. Many experts are calling for alternatives to gain-of-function studies to be utilized during the moratorium and are stating that guidelines should be clearly elucidated so that research can continue. Marc Lipstich,

an epidemiologist at Harvard T.H. Chan School of Public Health, has been particularly vocal in calling the research moratorium too broad as it limits work of flu surveillance and vaccine development (Reardon 2014). Researchers like microbiologist John Steel of Emory University are also concerned that long-term impacts could affect their ability to secure new grants and even end their academic careers.

The implications of this moratorium extend beyond research facilities and labs. Bill Sheridan, senior vice president of BioCryst Pharmaceuticals in Durham, North Carolina, notes that “private companies’ research on antiviral drugs and vaccines will also grind to a halt if some gain-of-function research is not allowed to proceed, because drug development is financially risky” (Reardon 2014).

The decision comes at an especially crucial time given the current panic around the spread of the Ebola virus. The West African Ebola virus outbreak has reminded researchers about the difficulties of finding and developing vaccines.

Though human trials for a vaccine have been ongoing since September 2014, there is no guarantee that treatments will be successful. The International Union of Microbiological Societies has suggested that risks must be taken to conduct gain-of-function research on the Ebola virus in order to develop more treatment options (Bamford and Shaw 2014).

The debate rests on whether the potential risks to the public are worth the benefit to be had from an increased understanding of influenza virus biology. In December 2014, a two-day meeting was held at the National Academy of Sciences in Washington, D.C. to discuss whether gainof-function research would be an appropriate approach to developing a vaccine for Ebola. It is expected that a statement will be made throughout these talks in regards to future virus research. These debates will continue to shape virus research in the future (Greenfieldboyce 2014).

References

Bamford, C., and A. Shaw. 2014. “We’ll never find an Ebola vaccine without taking some risks.” The Conversation, August 5.

Fidler, D. 2013. “It’s baaack! The biosecurity controversy over “gain-offunction” research on influenza viruses returns.” Arms Control Law, August 8.

Greenfieldboyce, N. 2014. “Scientists debate if it’s OK to make viruses more dangerous in the lab.” National Public Radio, December 16.

Ledford, H. 2013. “Scientists call for urgent talks on mutant-flu research in Europe.” Nature, December 20.

McNeil Jr., D. G. 2014. “White House to cut funding for risky biological study.” The New York Times, October 17.

Reardon, S. 2014. “Viral-research moratorium called too broad.” Nature, October 23.

Roos, R. 2013. “Scientists seek ethics review of H5N1 gain-of-function research.” University of Minnesota, Center for Infectious Disease Research and Policy, March 29.

Bioethics in Brief

Canada to Follow in American Footsteps?

Pending Gene Patenting Trial information to make a profit must appropriately compensate the patent holders, who are trying to regain the invested funds and ultimately turn a profit themselves (Ledbetter 2008).

From CHEO’s standpoint, its lawsuit stands to question not only the patenting of long QT syndrome, but also the unfair restriction of patients’ access to their own information and the advancement of clinical care. Development of genetic therapies against the fatal conditions that long QT syndrome can cause is just one struggle among thousands that should be conducted without the fear of being sued for patent violations (Crowe 2014). Similar reasoning fueled the 2013 U.S. Supreme Court ruling against the legitimate patenting of products of nature, abolishing gene patents on BRCA1 and BRCA2, genes that can increase the risk of familial breast and ovarian cancer up to 80%. Since the patent was abolished, treatments for the mutations that cause an increased risk of breast and ovarian cancer have become less expensive and more accessible to the patient population (Fisher 2013).

The Canadian Supreme Court has many ways to rule on the issue, including absolute invalidation of gene patents or the narrowing of the patents’ parameters to specific aspects of the gene, such as the right to manipulate or conduct tests without regulation. The case is on track to go to trial, but it is unclear when it will be heard. It will be interesting to see whether Canada follows the path of the U.S. Supreme Court in invalidating gene patents, or whether another solution is found.

References

Allen, K. 2014. “Gene patent lawsuit aims to clear up confusion in Canada.”

Toronto Star, November 3.

Crowe, K. 2014. “U.S. gene patents: patient care stymied in Canada - hospital claims.” CBC News, November 3.

Dube, D. 2014. “CHEO launches legal fight over patented genes.”

Ottawa Sun, November 3.

Fisher, D. 2013. “Patenting genes in Canada.” Biotechnology Focus, June 5.

Goddard, J., and Z. Glantz. 2013. “Association for Molecular Pathology vs.

Myriad Genetics Inc.” Cornell Legal Information Institute, April 15.

Ledbetter, D. 2008. “Gene patenting and licensing: The role of academic researchers and advocacy groups.” Nature, March 4.

Penn Bioethics Journal

In November 2014, the Children’s Hospital of Eastern Ontario (CHEO) in Canada filed a case against the U.S. patent holders of five patents on genes associated with long QT syndrome, a heritable heart rhythm disorder which can lead to fainting, seizures, and sudden death. This marks the first time Canadian courts have seen a direct challenge to the patentability of genes, on which the U.S. Supreme Court ruled in the 2013 well-publicized Association for Molecular Pathology v. Myriad Genetics, Inc. This case concerned the patenting of the BRCA1 and BRCA2 genes, and the Supreme Court ruled in favor of the Association for Molecular Pathology, effectively banning the patenting of genes in the U.S. (Fisher 2013, Goddard and Glantz 2013). The outcome of the Canadian case is similarly expected to establish a precedent for gene patenting in the country.

Since the early 2000s, Canadian gene patents have been passed without stringent regulation, since they were seen as unenforceable and invalid efforts to privatize and isolate genetic material. This case arose because CHEO believes that it has the capabilities to design and administer a diagnostic screening test for long QT syndrome that costs less than half of the current $4500 USD sticker price on a similar testing procedure. However, CHEO requires restricted access to the gene patents that are currently held by the University of Utah, Yale University, and Genzyme Genetics (Dube 2014).

Furthermore, long QT syndrome is just one of thousands of genetic conditions, so the greater issue at hand is not the ownership of these five gene patents, but the precedent this case creates for genetic ownership and genetic privatization (Allen 2014).

However, proponents of gene patenting argue that the patentability of genes is crucial to encouraging research and development focused on the causes and therapies for genetic diseases. Biotech firms are more willing to invest tens of millions of dollars into researching these diseases if they know they can patent their major findings and protect their efforts from being exploited by a third party. The patent protects the genetic findings, such that anyone who wants to use that

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Bioethics in Brief

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Vanguard Consultancies Strengthen Bond between Bioethicists and Scientists

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In the past decade, bioethics consultancies have emerged in a burgeoning bioethics field. These consultancies provide counseling to research and clinical scientists who encounter ethical complications (Dolgin 2014). Since the 1940s, scientists have submitted their research proposals to an institutional review board (IRB), also known as an independent ethics committee. After their proposals receive approval from an IRB, scientists are able to start their research. However, they cannot foresee all ethical issues that may arise, like the discovery of unexpected data during an experiment or trial. Prior to bioethics consultancies, scientists made realtime ethical decisions, often with neither the appropriate background nor expertise. These emerging consultancies principally enable contact between ethicists and scientists throughout the duration of a research study.

Consultancies balance strict regulatory processes, adhered to by the IRB, with informal, individualized ethics guidance.

“Unlike IRBs, consultants can provide guidance throughout a study — not just at the point of regulatory review — and do so in a non-confrontational advice-giving capacity. They offer an open space for talking about research ethics in a way that is not driven by the regulatory environment,” states Dr. Marion Danis, chief of the bioethics consultation service at the National Institute of Health Clinical Center in Bethesda, Maryland (Genetic Literacy Project 2014).

Because consultancies need not follow institutional, federal, or other regulations, they may also address ethical issues on differing scales. Their larger domain includes “mundane matters of informed consent and study protocol to controversial topics such as the use of experimental Ebola treatments” (Dolgin 2014). They then can create more practical or more creative solutions, in contrast to a regulated IRB. Bioethicist Steven Miles of the University of Minnesota in Minneapolis suggests that consultancies augment ethics knowledge in addition to the required IRB proposal. “For innovative research designs,” he states, “you need some independent person to say, ‘Well, let’s step back and think about this not just from the standpoint of do the regulations permit it, but does it fulfill the spirit of what people want done with the public research enterprise?’” (Genetic Literacy Project 2014).

Others, however, contend that for-profit consulting forsakes a bioethicist’s purpose: to answer questions of moral philosophy. For example, pharmaceutical companies employ bioethicists in clinical studies. Pairing these companies with bioethicists promotes divergent purposes: profit versus a supposedly “altruistic or advocative calling” (Rasmussen 2006). That a consulting bioethicist chooses to receive money for services may betray the bioethics field. The bioethics field and practitioners within it thus bear a changed moral obligation and responsibility. Furthermore, since companies receive ethics consulting, which is non-binding, bioethicists may deliver guidance through a different lens. They indeed might loosely interpret moral philosophy to satisfy the wants of a company. These and other administrative concerns explain why the NIH eliminated funding for a bioethics working group, which would assist ethics-consultation services and advance best practices for the profession (Dolgin 2014).

Despite this setback, bioethics consultancies continue to grow in size and standing. Benjamin Wilfond, director of the Treuman Katz Center for Pediatric Bioethics at Seattle Children’s Hospital in Washington, implemented the Clinical Research Ethics Consultation Collaborative without initial NIH funding. Under his lead, 35 bioethicists presently work together to improve the consultation service model (Dolgin 2014). Wilfond’s persistence in the Katz Center’s creation highlights the budding establishment of consultancies. The NIH has seemingly taken notice of these efforts to promote the bond between research and bioethics by creating new opportunities for such efforts to receive NIH funding (Fogarty International Center 2014). These consultancies will prove fundamental in strengthening and galvanizing this bond in the near future.

References

“Bioethics consulting services provide valuable oversight for researchers.”

2014. Genetic Literacy Project, October 28.

Dolgin, E. 2014. “Does your average scientist need an ethicist on call?”

Scientific American, October 21.

“International research ethics education and curriculum development award (bioethics).” 2014. NIH - Fogarty International Center - Advancing Science for Global Health, December 18.

Rasmussen, L. 2006. “Bioethics consultation for pharmaceutical corporations.”

American Medical Association Journal of Ethics, February 1.

Bioethics in Brief

Three-Parent Babies: A Debate of Eugenics future of designer babies and consumer eugenics” (Stein 2014). King’s organization, the Human Genetics Alert, argues that social benefits of mitochondrial-replacement therapy are driving proponents of the technique, rather than medical benefits (Human Genetics Alert 2012). For example, although less ethically charged methods such as egg donation exist, proponents of mitochondrial replacement argue that these methods do not provide the child with any of the mother’s genes. In addition, some proponents point out that mitochondrial-replacement therapy could open the door for lesbian couple conception, allowing them to conceive a child with genetic material from both female parents (Morgan 2012). The Human Genetics Alert believes that such social benefits should not be considered over the medical well-being of the child. Other opponents, like evolutionary biologist Klaus Reinhardt, also fear the possibility of “language” gaps in the genetic code for future generations caused by the mitochondrial and nuclear DNA not complementing each other (Weintraub 2014). Not enough is understood about the interactions between mitochondrial and nuclear DNA, and all future offspring of a baby created through mitochondrial replacement therapy would be vulnerable to any issues stemming from having a different source of mitochondrial and nuclear DNA. While the FDA has not stated a timeline to issue an edict for clinical trials, British Parliament is close to voting within the coming months on whether to allow mitochondrialreplacement therapy (Tingley 2014). Should Parliament pass legislation allowing the therapy, this would mark a watershed event in eugenics not seen since the United Nations’ agreement not to alter the human genome 15 years ago (Weintraub 2014).

References

Human Genetics Alert. 2012. “Human genetic engineering on the doorstep: the threat of ‘mitochondrial replacement’ techniques.” London: Human Genetics Alert Publications, November.

Morgan, J. 2014. “New DNA breakthrough will not lead to lesbian designer babies.” Gay Star News, June 4.

Sample, I. 2014. “Procedure to create babies with three people’s DNA could be legalized in April.” The Guardian, July 22.

Stein, R. 2014. “Combining the DNA of three people raises ethical questions.”

National Public Radio, November 10.

Tingley, K. 2014. “The brave new world of three-parent I.V.F.” The New York Times, June 27.

Weintraub, K. 2014. “FDA weighs risks of 3-person embryo fertilization.”

USA Today, February 24.

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The possibility of creating a baby with a genome comprised of genetic material contributed by three individuals has prompted responses in the past year from both the United States Food and Drug Administration (FDA) and the British Parliament. This new possibility of introducing a third parent’s genetic material stems from the mitochondria in our cells containing a small genome completely separate from the DNA in the nucleus. While nuclear DNA of a child comes from both of his or her parents, the 37 genes in mitochondrial DNA are inherited only from the mother, who contributes the mitochondria-containing cytoplasm of the fertilized egg.

New therapies seek to prevent mitochondrial diseases like muscular dystrophy by replacing the mother’s mitochondrial DNA with another woman’s healthy mitochondrial DNA in vitro before fertilization (Tingley 2014, Sample 2014).

The first successful pregnancy of a “three-parent baby” occurred in August 1996 at the St. Barnabas Medical Center in New Jersey (Tingley 2014). In this case, the older technique of cytoplasmic injection was used, in which cytoplasm of the second woman’s egg is inserted into the mother’s egg. Seven documented clinics reportedly used the same technique of cytoplasmic injection until 2001, when the FDA declared that insertion of an egg’s cytoplasm into another egg requires an Investigational New Drug (IND) application for use in humans (Tingley 2014). Recently, Shoukhrat Mitalipov, the U.S.’s preeminent researcher in the field, has stirred up ethical debates with an improved mitochondrial-replacement therapy technique he used to birth five monkeys (Weintraub 2014). Rather than simply injecting cytoplasm, this method specifically pairs the mitochondrial DNA of a healthy egg with the nuclear DNA of the affected mother’s egg (Tingley 2014).

This past February, the FDA held a conference to investigate the implications of conducting clinical trials on humans.

Leading the discussion in favor of the technique, Mitalipov claims, “[w]e want to replace these mutated genes, which by nature have become pathogenic to humans” (Weintraub 2014). Other supporters of the technique, such as England’s Chief Medical Officer, Dr. Sally Davies, state that only 37 mitochondrial genes would be eligible for replacement, leaving intelligence, physical appearance and behaviors unchanged (Stein 2014).

Yet, others such as David King, a British molecular biologist active in the Human Genetics Alert group, fear the effects on society, stating that it “can potentially lead to this

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Bioethics in Brief

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NIH Releases New Genome Sharing Policy

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In August 2014, the National Institutes of Health (NIH) released the Genomic Data Sharing (GDS) policy, which governs how genomic data from NIH-funded projects are shared and made accessible to the public. This policy had been long-awaited in light of the range of ethical concerns, from privacy risks to patient autonomy, raised by the publication of genomic data.

The GDS policy introduces several new measures that protect patient autonomy while maintaining incentives to collaborate by sharing data. In the GDS policy, informed consent is now required to include permissions for the widest possible sharing and use of patients’ data, whether it be genomic data or cell lines and tissue samples. The consent must also explicitly indicate if the data will be openly shared or will be limited to controlled access, which is given on request and must be renewed annually. In addition, informed consent is now required even for samples that will be stripped of identifying information. In a study published in Science in January 2013, researchers were able to identify anonymous donors from public genome databases, highlighting the inherent privacy issues in genomic data sharing (Erlich 2013).

To promote collaboration, the policy also requires researchers to publish their data online before its publication in a manuscript or within six months of initial data submission.

While the revisions to the informed consent of study participants better protect patient autonomy, the privacy risks inherent in genomic data sharing still exist.

While the new GDS policy promotes collaboration, sharing, and patient autonomy, there are differing opinions on several aspects. For example, Heather Pierce, senior director of science policy at the Association of American Medical Colleges (AAMC) in Washington D.C., hoped that, in addition to wider informed consent, “the NIH would recognize dynamic consent, which allows an individual to broaden their consent in the future, or have choices [to give permission for particular research uses] along the way” (Noorden 2014). Also,

while stronger informed consent measures provide greater protection for study participants, the AAMC has voiced concerns that this may place an undue burden on researchers and institutions (AAMC 2013). Another cause of concern for researchers is the data sharing deadline that is six months from collection, which some worry makes researchers vulnerable to others “stealing” their research before it has been formally published. Yaniv Erlich, a computational biologist at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, is also worried that data involving rare diseases might not be shared, as the data-sharing policy does not apply to studies performed on less than 100 genomes (Noorden 2014). The GDS has areas of concern for many in the field.

Even if some aspects of the GDS are a cause for concern, the need for such a policy is clear. Dr. Eric Green, co-chair of the committee developing the GDS policy, points out that “advances in DNA sequencing technologies have enabled [the] NIH to conduct and fund research that generates ever-greater volumes of GWAS and other types of genomic data” (NIH 2014). These developments only increase the importance of a thoughtful and thorough data sharing policy. The hope is that these measures, along with others included in the new GDS policy, will provide an effective and ethical guide to genomic data sharing for years to come.

References

AAMC. 2013. “AAMC comments on NIH’s draft Genome Data Sharing policy.” Association of American Medical Colleges, November 22.

Erlich, Y. 2013. Identifying personal genomes by surname inference.

Science 339: 321-24, January 18.

Harmon, A. 2010. “Indian tribe wins fight to limit research of its DNA.” The New York Times, April 21.

NIH. 2014. “NIH issues finalized policy on genomic data sharing.” U.S National Library of Medicine, August 27.

Noorden, R. V. 2014. “US agency updates rules on sharing genomic data.”

Nature, September 01.

Paltoo, D. N. et al. 2014. “Data use under the NIH GWAS data sharing policy and future directions.” Nature Genetics 46: 934-938, August 27.

Bioethics in Brief Contributing Writers John George Armstrong Stephen Cho Andy Guo

Ruchita Pendse Samip Sheth Girish Valluru

Interview

A Conversation with Dr. Matthew Mendlik Dr. Matthew Mendlik is an Assistant Professor of Clinical Neurology and an attending physician on the Palliative Care Service at the University of Pennsylvania, with interests in chronic pain, headache, and general and Neurologyspecific Palliative Care. He graduated from Ohio State University College of Medicine and completed his residency in Neurology at Boston Medical Center. Following this, he was a Geriatric Neurology and Palliative Care fellow in the Boston VA Healthcare System before completing his training in the Harvard Palliative Medicine fellowship.

Penn Bioethics Journal (PBJ): Could you describe your career journey and interest in neurology and palliative care?

Dr. Matthew Mendlik (MM): In medical school, I observed one of the residents on my neurology rotation lead patients and families in difficult discussions with skill and compassion. She ended up in Ohio State’s Palliative Care fellowship, and I rotated on that service, which was led by a neurologist. These experiences not only showed me that a neurologist could be a palliative care physician, but suggested that it was an excellent, and needed, combination. Through residency, the experiences that really drew my attention were those that involved communication about illness, complex medical decision-making, and end-oflife care. I was lucky to have an attending physician tell me to “follow my heart” after a grueling two weeks of night shifts, as she witnessed my distress over career choices, and I decided then and there that my career would be in palliative medicine. At Penn, I’ve been fortunate to be part of quite a bit of crossover between neurology and palliative care. The majority of my work is palliative care, but I also have a weekly neurology clinic and teach medical students and neurology residents, particularly about issues related to palliative care.

PBJ: One of the major issues for PVS or MCS patients is the interaction between the medical team and the patient’s family members. How do you best mediate that relationship?

MM: I attempt to help staff and families consider what it would be like to be lying in a bed, unable to communicate but able to hear and understand events around them. Imagining themselves

MM: The lack of ability to know what is being understood by patients without the ability to communicate is often and understandably the major focus of these patients’ families.

There are many studies attempting to demonstrate and facilitate even basic yes/no ability by means of physical parameters like biochemical changes or signal detection in the brain. I think establishment of a means of basic communication via technology for those patients with no visually-apparent physical ability is a reasonable expectation in the next decade or so.

PBJ: What are some other important topics in neuroethics, or perhaps bioethics in general, that you typically encounter in your day-to-day practice? How do you integrate understanding of these ethical considerations into your clinical practice?

SJ: One of the most difficult issues I encounter in the care for patients with serious neurologic illness is how to care for a person who has suffered a devastating neurologic injury, who is then stable and not declining, continuing to eat but requiring continuous care and supervision. Thankfully these are rare, but there is a lack of resources and facilities to care for such patients.

These cases are particularly challenging when there are no close relatives who can give us a sense of what the patient might feel about his or her condition and what his or her wishes might be for continued care.

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MM: Advances in technology and our ability to investigate processes at the molecular and atomic levels, and just as importantly our computing ability and capacity to manage the vast amounts of data involved, will likely lead to a better understanding of what exactly is going on in the brains of patients in PVS or MCS. Functional MRI is already showing us real-time changes in brain activity; it’s not impossible to imagine this ability increasing over time to begin to show thoughts in a visual way to observers. One could further imagine the implications this has for discovering the thoughts of patients whose bodies are no longer able to provide a means of communication to others. Neuroimaging may at some point show us not only that patients in PVS and MCS are having thoughts, but perhaps even what those thoughts are about.

PBJ: In clinical practice, what are some of the other areas of unmet need in the treatment of patients in PVS or MCS? Realistically, what innovations might occur in the next five or ten years to address these unmet needs?

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PBJ: What impact could improvements in neuroimaging have on patients in persistant vegetative or minimally conscious states (PVS or MCS)?

in this situation naturally causes people to think about how they would wish to be treated — basics like being addressed personally, having their frustration at not being able to communicate validated, and being reassured that despite this, their family and doctors will continue to do the best they can for them. I try to foster the Photo courtesy of practice of addressing the patient directly Matthew Mendlik. as a participant in conversations, instead of a passive observer, based on the belief supported by many accounts that patients in those states can have the capacity to hear and understand.

Once staff and family are thinking this way together, mindful of how difficult the situation must be for the patient, they can keep themselves aligned with each other and focused on the patient.

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Interview

A Conversation with Dr. Steven Joffe

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Steven Joffe is a pediatric oncologist and bioethicist, and is currently the Emanuel and Robert Hart Associate Professor of Medical Ethics and Health Policy at the University of Pennsylvania Perelman School of Medicine. He serves as Director of the Penn Fellowship in Advanced Biomedical Ethics, Chair of the Children’s Oncology Group Bioethics Committee, and a member of the FDA’s Pediatrics Ethics Subcommittee. Dr. Joffe attended Harvard College, received his medical degree from the University of California at San Francisco, and received his public health degree from UC Berkeley. He trained in pediatrics at UCSF and undertook fellowship training in pediatric hematology/oncology at the Dana-Farber Cancer Institute and Boston Children’s Hospital.

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Photo courtesy of Steven Joffe.

Penn Bioethics Journal (PBJ): Could you tell us about your career trajectory and how you became interested in bioethics?

PBJ: What unique ethical responsibilities do pediatricians have, and perhaps what unique (ethical) challenges do they face, compared to other physicians?

Dr. Steven Joffe (SJ): My first rotation in medical school was on the neurology service at San Francisco General Hospital. We admitted a highly capable 90-year-old woman, who spoke only Spanish and had recently emigrated from Central America to the U.S. to live with her adult children, with new onset lower-extremity weakness, incontinence, and back pain. Her family told us that she had been diagnosed elsewhere a month before with inoperable stomach cancer, and at the family’s request, she hadn’t been told her diagnosis.

An MRI now showed a metastasis to the spine, which required urgent radiation therapy. Her family still insisted that she not be told about her cancer, but the treatment team felt that they needed to tell her and that only she could give consent for her radiation therapy. I watched fascinated as an extremely thoughtful radiation oncologist, herself a native Spanish speaker, navigated this delicate situation with the family. Ultimately, she was able to ask the patient if she wanted information and to make decisions, or if she wanted her family to get information and make decisions for her.

The patient wanted information herself, and so we were able to share the details, get her consent, and proceed with therapy.

SJ: Pediatricians face a number of unique ethical questions.

They have to navigate triangular relationships — doctor/ patient/parents — and figure out how to proceed when parents and children disagree. They have to decide how much to involve children in decisions about their own care, given differences in age, maturity, family and cultural context, etc.

Unlike competent adults who can make their own decisions based on their own values, parents and doctors have to make decisions for children, especially younger children, based on the child’s best interests — and agreeing on what’s in a child’s best interests isn’t always easy. They have to think about what decisions, such as some decisions about genetic testing, to defer now so that the child can make them when he’s an adult. And they are much more limited in the research they can do with children because we don’t allow children to volunteer, or to be “volunteered,” for high-risk research that doesn’t offer them the potential for benefit.

Between our third and fourth years, we did a one-week fulltime course in bioethics. I enjoyed it immensely and found the issues we discussed to be among the most interesting I’d encountered in med school.

I ultimately went into pediatrics, and then into pediatric oncology. In pediatric oncology fellowship, every day we encountered ethical questions — how to make decisions for and with a dying child, how to take care of children and do research on them at the same time, how to work with a family that didn’t want to tell their child her diagnosis. I began conducting research on ethical issues in childhood cancer research, and have continued to work on these and other related questions ever since.

PBJ: One of your main research areas focuses on the return of individual genetic results and incidental findings to participants in genome-wide association studies. Are current guidelines followed in practice, and how could they be improved, particularly for pediatric patients?

SJ: There’s no easy answer to this question, for several reasons. Guidelines are new, and there’s a fair bit of disagreement about them, so there’s not really a standard of care just yet1. Second, I don’t think we have good data on what investigators or labs are doing in practice. I think the most important way in which we can improve practice, for both kids and adults, is to clearly explain to research participants or their parents during the process of consent exactly how we plan to handle any individual genetic results or incidental findings.

A Conversation with Dr. Steven Joffe PBJ: Outside of a research setting, some patients choose to purchase direct-to-consumer genetic tests. How should physicians consider results from these tests?

SJ: This is another unsettled area. If there’s a result from a DTC genetic test that has clear medical implications, then physicians need to explain the potential implications, recommend confirmatory testing in a clinical lab, and then take appropriate actions based on the test result. But there are lots of results from DTC genetic tests that don’t have clear medical implications, and my personal view is that physicians don’t have an obligation to address these with patients. One major challenge in this area is there aren’t nearly enough physicians with sufficient expertise in genetics, or genetic counselors, to meet the increasing need to advise and guide patients in these areas. It’s an urgent need, and my hope is that physicians who are currently in training, whatever field they ultimately go into, will be much more sophisticated about genetics than my generation is. We also need high-quality resources, easily available on the web, to guide physicians in managing genetic test results and conditions.

PBJ: As patients are exerting more influence in treatment decisions, what ethical questions arise when considering other direct-to-consumer appeals, such as those for experimental oncology treatments and clinical trials?

SJ: My list will be incomplete. Some of the most active debates right now concern the definition of death, which has important implications for when it’s ethical or legal to remove organs for transplantation2, and also for when lifesupport interventions can be withdrawn especially in the setting of disagreement between hospital and family. We’re also seeing an expansion in the last few years of willingness among the states3 to legalize physician-assisted suicide (PAS), and as experience accumulates and the country becomes more comfortable with it, I think PAS will expand. There are vigorous debates around how to control costs in health care, with two particular areas of emphasis. The first is on what we should do about low-value care, by which I mean care that offers patients some benefit but at significant cost.

The second is what to do about very high-cost therapies, some of which offer patients significant benefits but at the cost of hundreds of thousands of dollars a year. Another is how to navigate the balance between patients’ privacy rights and right to control information about them in electronic databases, electronic medical records, etc., vs. the potential public good that might come from mining that information among very large numbers of patients to improve the quality of and evidence underlying treatment. Finally, medicine is currently rethinking how we can integrate research, including randomized trials, into the practice of medicine in the context of what has come to be called learning health care systems4.

My advice to students who want to tackle these or other questions is to identify a question that grabs you, that you care a lot about, and then figure out who’s working on it. Ask him or her how you might be able to address it. But make sure you really understand what’s going on in the field, that you understand what the questions or challenges are from the perspective of the people — doctors, scientists, or patients and families — who actually confront it in their daily work or lives. There’s no substitute for becoming informed, firsthand, about the realities and nuances of the issue you want to address.

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The American College of Medical Genetics published guidelines suggesting that DTC genetic testing protocols include a physician upon the “ordering and interpreting [of] a genetic test,” that the consumer be fully informed of the implications of the test on their health and of the science behind the test, and that the consumer understand privacy risks and concerns regarding their genetic information. The Presidential Commission for the Study of Bioethical Issues also published recommendations in 2013 with an emphasis on what to do in the case of incidental findings. Overall, the commission recommends that consumers be informed of the possibility of such findings, that guidelines be developed in the case of incidental findings, and that research be funded to measure “potential costs, benefits, and harms of incidental and secondary findings.” For further reading, please see http://bioethics.gov/node/3186 2 For more information on, please read: Rubenstein, A., E. Cohen, and E. Jackson. 2006. “The definition of death and the ethics of organ procurement from the Deceased.” The President’s Council on Bioethics.

3 Physician Assisted Suicide has been legalized in Oregon via the Death with Dignity Act (1997), in Washington via the Washington Death with Dignity Act (2008), in Vermont via the Patient Choice and Control at End of Life Act (2013), and in Montana and New Mexico via court rulings (2009 and 2014, respectively).

4“ Learning healthcare systems are those that emphasize a collaborative approach that shares data and insights across boundaries to drive better, more efficient medical practice and patient care.” For further reading, see: NIH Health Care Systems Research Collaboratory. “Learning healthcare systems.” In Rethinking Clinical Trials: A Living Textbook of Pragmatic Clinical Trials.

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SJ: Physicians need to remember the ethical foundations of their relationships with patients — to advise patients and act in ways that promote their wellbeing and minimize harms to them, to engage them in respectful conversation, and to respect their decisions. They also need to contribute to the generation of high-quality evidence to improve treatment and inform practice, and to care for patients in ways that use limited resources wisely and efficiently. Keeping these and other related values in mind, physicians should be wellprepared to work with patients who bring questions like these. And we should welcome the fact that, very often, we work with patients and families who are well informed about their diseases and who bring their own information and ideas about treatment to their doctor. The fact that patients and families have such good access to information and to peers makes partnership in patient care much more of a reality than it ever has been in the past.

PBJ: What are some of the other important debates at the forefront of bioethics? What advice do you have for students who might be interested in getting involved in researching these questions in the future?

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Article

Direct-to-Consumer Genetic Testing An Examination of Privacy and Security Concerns Ameay Naravane‡ Since the genesis of the Human Genome Project, decreasing costs of DNA synthesis have allowed for an everincreasing role of genomics in the advancement of the biotechnology industry. One such genetic technology that has resulted from the biotech movement is direct-to-consumer (DTC) genetic testing, as exemplified by the market leader, 23andMe. DTC genetic testing, however, has created several ethical, health, and security concerns on an individual, industrial, and societal level. First, DTC genetic testing may result in individuals misinterpreting DTC results. Second, the DTC genetic testing industry remains largely unregulated, which has led to false advertising within the industry. Moreover, weaknesses in the industry’s data protection and third party disclosures limit the privacy protection of individuals using their services. Finally, DTC genetic testing raises ethical concerns on a societal level, as the genetic data obtained by DTC genetic testing companies is being used for long-term medical research. Given such significant concerns, the lack of cohesion in the government’s regulatory approach is troubling.

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Introduction

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Recent advances in the biotechnology industry have allowed for important developments that have the potential to improve the quality of life for many. However, these technologies also come with associated risks. One such technology is direct-to-consumer (DTC) genetic testing, which allows consumers to personally order and receive genetic test results. While genetic testing itself is not new, it has only recently become directly available to consumers through companies such as 23andMe. An exploration of the DTC genetic testing industry suggests that this new technology has several concerns on individual, industrial, and societal levels. Unfortunately, current regulation does not address these concerns, there are few pending changes to do so, and the lack of regulatory cohesion has proven to be an ineffective method to ensure protection of individuals and populations.

However, the FDA has established certain regulations for major DTC companies. As of November 2013, the FDA has banned the DTC company market leader, 23andMe, from continuing to provide consumers with DTC genetic tests, and the company has now shifted its focus to serving as an ancestry database until further notice. However, the FDA ban does not prevent 23andMe from using the genetic data it already acquired in research studies. In fact, the NIH recently provided 23andMe with 1.4 million dollars to increase the size of the 23andMe gene database (Farr 2014). Because the data has already been collected, it is compatible with the FDA ban. This new grant from the NIH demonstrates that agencies within the federal government itself are not working in tandem. Although the FDA believed that ‡ Georgetown University, avn2@georgetown.edu

the scientific basis for the genetic tests was too shaky to provide accurate results to the consumers, the NIH has demonstrated that it values 23andMe’s research. Since DTC genetic testing companies are operating in a relatively new and unregulated market, as the market continues to grow, privacy and ethical concerns will grow as well. As such, it is important to examine the concerns with the market today so that we are well prepared for potential harms in the future.

Background: The DTC Genetic Testing Process The DTC genetic testing process can be condensed into three simple steps: choosing a DTC company, providing a saliva sample, and receiving an analysis of the genetic information by the DTC company.

Although the front runner in the DTC industry was 23andMe prior to the FDA’s ban, there currently are several DTC companies at the head of this market. Generally, DTC companies offer three different services: testing for one condition in particular, testing for multiple mutations that assess an individual’s risk for certain diseases, and finally, genome wide sequencing that tests for hundreds of diseases (Swan 2010). After choosing a company, individuals must provide a DNA sample, typically in the form of a cheek swab or saliva, and then send that sample to a DTC company such as 23andMe. When DTC genetic testing companies conduct genetic analysis, they are actually looking for variations in the genetic code called single nucleotide polymorphisms (SNP).

A SNP can be thought of as a typo in a specific location of an individual’s DNA in which a single nucleotide is replaced by a different one. If a variation at a specific genetic locus exists in at least one percent of the population, it is

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Direct-to-Consumer Genetic Testing considered a SNP. Although a large majority of SNPs have no effect on an individual’s health, some SNPs have been associated with certain diseases and conditions. Because of this, DTC genetic companies can use laboratory techniques to see if an individual possesses specific SNP markers that are correlated with an increased likelihood of developing a particular disease (Schleckser 2013).

This SNP based approach to genetic testing is used because it is extremely cost efficient. Since the DTC companies know which SNPs are likely to correlate to which diseases, they do not need to sequence the entire human genome. However, this approach can also be somewhat misleading because SNPs are only one type of genetic mutation, and the DTC approach may fail to catch other types of mutations that may be more indicative of diseases (“Providing Your Saliva Sample”). After this analysis is complete, these results are then relayed to the consumer in a report.

Concerns Regarding DTC Testing on Individual, Industrial, and Systemic Levels A. Individual Level Concerns: Responsibility to Interpret And Implications of Interpretation

B. Industrial Level Concerns: Misleading Tests and False Advertising

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While the previous concerns were primarily at the individual level, DTC genetic testing also brings concerns at the industry level, related primarily to occurrences of misleading advertising and poor test quality. In fact, due to the limited regulation in the DTC genetic testing market and the low barrier to market entry, there are significant concerns about the quality of the tests offered in this industry (Hudson 2007).

A recent study conducted by the Government Accountability Office (GAO) had three major findings regarding the quality of DTC genetic tests (US GAO 2010).

First, the risk predictions of DTC companies sometimes directly conflict with the facts of the consumer’s actual illnesses and family medical history (Caulfield 2010). This once again speaks to the questionable scientific basis for the tests conducted by DTCs, as the tests are ultimately based on only one type of genetic mutation, SNPs.

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A major concern at the individual level is that upon receiving the results from the DTC genetic testing company, consumers may be misinformed about what their results actually mean (Critchley 2014; Yurkiewicz 2010). The American College of Medical Geneticists recently recommended that DTC genetic companies should better explain what these tests actually mean in regards to consumers’ health (ACMG 2008). Currently, DTC companies simply inform consumers about the probabilities of potential risks associated with any given disease. However, they do not mention that the analysis of DTC tests is highly nuanced (ACMG 2008). This information needs to be relayed to consumers in a lucid manner so that consumers know that their genetic reports show potential risk and that they cannot provide a definitive diagnosis (ACMG 2008). It appears that DTC companies are taking steps to aid customers in the interpretation of their genetic data. In fact, 70% of DTC genetic testing websites recommend that consumers reach out to their healthcare providers to interpret the results (Singleton 2012).

However, even if consumers were to visit their physicians — the current recommendation of most DTC genetic companies — these visits do not seem to be useful for several reasons, including the awareness and knowledge on the part of the clinician (McGuire 2009). While 78% of those who receive a DTC genetic test said that they would ask their physician to interpret the results (McGuire 2009), the general practitioners in the American healthcare system are ill-equipped to analyze DTC genetic testing results, as their knowledge of genomics-based research is limited (Bloss 2011). Moreover, even genetic counselors who are specifically trained to analyze genetic tests feel underequipped to explain the ideas of genetic testing to the average person (Schleckser 2013).

Despite the consumer interest in DTC genetic testing, its clinical utility has not been demonstrated; indeed, there is little scientific evidence that links DTC genetic testing to healthcare benefits (Caulfield 2010). This is in part due to the fact that the most cost efficient and most common DTC tests are not thorough — they look for SNPs, which are only one type of genetic mutation. As a result, the tests ignore the vast variety of genetic mutations that exist. Moreover, even if DTC genetic tests had a solid scientific basis, sometimes there is little clinical action that can be taken to prevent a disease from occurring (Caulfield 2010). If the test indicates that an individual may be at a higher risk for developing breast cancer, the individual may be able to increase the frequency of check-ups with a doctor. However, if DTC genetic testing indicates that an individual may be at a higher risk of Alzheimer’s disease, there is little the individual can actually do with modern medicine to prevent the development of this disease (Lewis 2011). The health benefits of DTC testing are typically lifestyle changes that patients have already been recommended, but which health promotion and disease prevention efforts have not been able to impact. More importantly, there is little evidence that individuals who receive DTC testing actually use the results to make a “sustained behavior change” in response to the results of their DTC test (Caulfield 2010).

Overall, this indicates that the healthcare system is not yet prepared to deal with the rise in DTC genetic testing, let alone the advances in personalized genomic medicine.

Since the current healthcare system has a limited capacity to provide information about genetic tests, consumers are left with potentially false information that they have no way of verifying. Although increasing physician awareness of genomics based research may help both clinicians and consumers to better understand the results of DTC testing, there is clearly a need to fill the void of genomics knowledge in the healthcare system.

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Direct-to-Consumer Genetic Testing Second, GAO showed that the information within the same report given to consumers was contradictory.

For example, one of the fictional customers received a “clinical report” predicting that the individual was at belowaverage risk of developing celiac disease, and on the other hand received a “research report” suggesting that the same individual was at above-average risk for celiac disease (Kautz 2010). This is a major issue as it can be confusing for patients to properly interpret these two conflicting findings.

Finally, the GAO found that several DTC companies had endorsed supplements that were scientifically invalid.

For example, one company marketed one supplement as being able to “repair damaged DNA”, which scientists confirmed as an unfounded claim (Kautz 2010). This type of false advertising can be dangerous to the consumer not only because it can promote the use of potentially harmful supplements, but also because it can foster hope when the supplement is in fact ineffective in curing or preventing diseases. The findings of the GAO reports suggest that there is a significant amount of fraud occurring in the DTC genetic testing industry, that many of the findings do not have vigorous scientific backing, and that there needs to be greater regulation of DTC genetic testing.

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C. Industrial Level Concerns: Data Security and Third Party Disclosures

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Another area of concern at the industrial level relates to information security issues such as accidental data breaches. A recent study suggested that there is a potential for accidental data breaches during transmission of genetic information.

In fact, in the past, 23andMe has accidentally sent data of up to 96 individuals to the wrong customers–a serious and potentially quite harmful occurrence (Gruber 2014). Given the sensitive nature of genetic information, it is of great importance that such data breaches do not happen.

This is especially concerning because additional studies have shown that genetic data can be re-identified using publicly available data. In one study, researchers were able to match 84% of de-identified genomes to public profiles on the genome project website using a program called Reidentification of DNA (REID) (Sweeney 2013). Another study also explains that many hospitals release anonymous collections of DNA along with demographic information such as an individual’s zip code, gender, and date of birth, and using such data in connection with local census data can identify an individual (Malin 2001). Thus, if DNA data from a DTC genetic testing company were accidentally leaked or released to a third party, there is a strong possibility that this individual could be re-identified.

Although DTC companies are concerned with the issue of accidental data breaches, they reserve the right to engage in third party disclosures. For example, on the 23andMe website, the company maintains in their terms and services section that they have the right to third party disclosures of the genetic information of all customers who provide them with their genetic information (“Terms and Service”). DTC

genetic companies legally maintain the rights to a customer’s data. This is of particular concern because it means that the company can sell the individual’s genetic information to third parties ranging from insurance companies to pharmaceutical companies. Moreover, if a DTC genetic company went bankrupt and was acquired by another company, the customer’s data would be transferred to the acquiring company (Gruber 2010). Thus, there exists potential for discrimination and stigmatization if the consumers’ genetic data was given to a third party (Hogarth 2008).

Part of the long term concern with companies such as 23andMe maintaining rights to their consumers’ genetic information is the lack of clarity with regard to their use of this vast amount of information. 23andMe plans to use the massive amounts of information collected to conduct medical research. Given the sheer number of individuals whose genetic information they can access, they can look for similarities between different genomes to try to determine the genetic sequences that may cause certain genetic conditions.

Such intentions are benevolent, but 23andMe’s strategy to obtain this data seems questionable.

In the methodology section of a recent paper that used data from 23andMe, researchers explained that they were granted exemption from a commercial Institutional Review Board (IRB) because the research conducted in that study was “performed on anonymized data with no contact between investigators and participants [and] does not constitute research on human subjects” (Eriksson 2010).

This commercial IRB’s exemption is somewhat concerning because an IRB is in charge of ensuring that human subjects are protected, and control over one’s genetic information is part of an individual’s exercise of autonomy. This is even more troubling given the ability of programs such as REID to re-identify patients. These industrial level concerns are significant because accidental data releases have the potential to lead to re-identification of sensitive information, which ultimately poses a privacy concern to individuals.

D. Societal Level Privacy Concerns: Lack of Informed Consent and Lack of Transparency With these privacy concerns in mind, transparency becomes especially crucial in the DTC genetic testing industry for two reasons. First, the industry itself is minimally regulated, and second, the results reported by a DTC company are highly subjective, as they are based on probabilities. Transparency is important so that individuals know the methodology used and can avoid misinterpretation (Yurkiewicz 2010). On the one hand, it appears that 23andMe’s terms and services section on their website has some information such as potential privacy concerns, limitations of current regulation, risks of data breaches, and third party disclosures. Its terms of service even explain the medical research they conduct and say that only data from consenting individuals is used for research (Eriksson 2010). In fact, a recent study analyzing the transparency of the DTC market reported that 23andMe meets 92% of the transparency standards of the American

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E. Society Concern: Dilapidated LegislationHIPAA (1996) and GINA (2008)

Conclusion and Consumer Recommendations In summary, although DTC genetic testing has great potential to provide consumers with important information about their health, there are significant concerns related to DTC testing on the individual, industry, and societal levels that call for increased regulation. If further steps to regulate the DTC genetic testing industry are not taken soon, the industry may pose further security and privacy violations to

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The two major pieces of legislation that are related to the issue of DTC genetic testing are the Health Information Portability and Accountability Act (HIPAA) of 1996 and the Genetic Information Nondiscrimination Act (GINA) of 2008. The major result of HIPAA was the creation of what is now called “the privacy rule” that frames the confidentiality between a patient and his or her doctor in legal terms (Caufield 2011). While HIPAA has proven to be useful in direct service healthcare, its application to other medically related situations is limited. According to the American Society of Human Genetics, “DTC companies are not necessarily subject to the health privacy regulations issued pursuant to the [HIPAA], leaving consumers vulnerable to having their information used or disclosed in a manner that would be impermissible in the healthcare system” (as qtd. in Caufield 2011).

In fact, the purpose of the 2008 GINA was to close some of the loopholes that were left open under HIPAA. GINA addressed four major concerns: first, ensuring the privacy of medical records; second, rejecting mandatory preemployment genetic testing; third, ending disqualification of insurance or termination of employment due to misinterpretation of genetic information; and finally, preventing denial of insurance coverage for untested family members (Steck 2011).

The major accomplishment of GINA is that it prohibits discrimination based on genetic information in healthcare coverage and employment, in both the public and private sectors (GINA). However, as with HIPAA, GINA has several loopholes. Most importantly, the nondiscrimination policies of GINA do not include life insurance, disability insurance, and long-term care insurance (GINA). Additionally, there is a significant concern that individuals may have DTC tests conducted, and the DTC companies may leak this information to third parties like insurance companies and employers, as while these entities cannot require genetic testing, they can still obtain the information (Kautz 2010).

A simple first step to begin regulating the DTC genetic testing industry more effectively would be to streamline the current scattered regulatory approach to DTC genetic testing.

Currently, both the FDA and the Federal Trade Commission regulate the DTC genetic testing industry; however, this approach is ineffective and inefficient. The FDA has little control over individuals or companies who use the genetic test in ways that are not intended by the manufacturer of the genetic tests, as its jurisdiction is primarily based on making sure that the genetic tests are safe to the public (McGuire 2010).

However, the Federal Trade Commission seems uniquely positioned to regulate the DTC genetic testing industry.

The job of the Federal Trade Commission is to declare unlawful “unfair or deceptive acts or practices in or affecting commerce” (Hogarth 2008). Given the generally misleading nature of DTC genetic tests, it seems clear that it would be well within the jurisdiction of the FTC to most effectively regulate DTC genetic testing of the three agencies discussed so far. Ultimately, there would be two major benefits of FTC regulation. First, the more reputable DTC genetic testing companies would be incentivized to ensure that their product is advertised appropriately without vast exaggerations.

Second, and more importantly, FTC regulation would ensure that questionable products would be driven out of the market (Schleckser 2010).

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College of Medical Genetics (ACMG 2008). However, industry wide, the level of transparency is significantly lower — only 6 of the 25 companies in the industry met 70% of the American Society of Human Genetics (ASHG) transparency recommendations that this study analyzed.

This low level of transparency reflects the low priority given to informed consent in the DTC industry. One researcher commented, “DTC genetic testing industry […] is more interested in promoting sales than informed choices” (Yurkiewicz 2010).

This reality is further reflected in the fact that companies that comply with the transparency standards of the ASHG tend to comply in name only; the information required to make an informed decision is typically hard to find and is often only accessible after registering for a test (“Terms and Services”). Thus, although 23andMe does require an individual’s consent to use his or her genetic information in medical research, it is unclear whether the individuals are aware of the potential ramifications of consent, a concern that would be effectively handled if 23andMe was required to undergo IRB review. Much of the information on the websites of DTC companies simply provides disclosure without allowing for customer understanding (Lewis 2011).

For example, companies often provide citations offering “support” for the linkage between a gene and a disease, knowing very well that the average customer would not be able to interpret the article even if he managed to find it (Lewis 2011). Ultimately, what seems problematic in this situation is that it is unclear whether consumers ordering DTC tests fully understand the implications of their consent — particularly the potential for them to be reconnected to their supposedly “anonymous” private information.

Additionally, it is also clear that although the DTC genetic testing companies have the correct information in their terms and conditions section, consumers are not likely to actually read the fine print.

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Direct-to-Consumer Genetic Testing its consumers. In the meantime, consumers can do two things to protect themselves from potentially harmful situations.

First: read the fine print. Although it may be tedious, the potential lack of privacy should motivate consumers to attempt to really understand the DTC genetic testing process in order to make an informed decision. Second, consumers should evaluate whether a DTC test will be clinically helpful for them or whether they are taking the test simply for fun.

If it is the latter, let buyers beware: their highly sensitive personal data may not be so personal anymore.

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References

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American College of Medical Genetics. 2008. “ACMG statement on directto-consumer genetic testing.” Bethesda, MD: American College of Medical Genetics.

Berg, C., and K. Fryer-Edwards. 2008. “The ethical challenges of direct-toconsumer genetic testing.” Journal of Business Ethics 77(1): 17-31.

Bloss, C. S., N. J. Schork, and E. J. Topol. 2011. “Effect of direct-to consumer genomewide profiling to assess disease risk.” New England Journal of Medicine 364(6): 524-534.

Caulfield, T. et al. 2010. “Direct-to-consumer genetic testing: good, bad or benign?” Clinical Genetics 77(2): 101-105.

Caulfield, T. and A. L. McGuire. 2012. “Direct-to-consumer genetic testing: perceptions, problems, and policy responses.” Annual Review of Medicine 63(1): 23-33.

“Consumer Information.” 2014. Direct-to-Consumer Genetic Tests. Federal Trade Commission.

Critchley, C., D. Nicol, M. Otlowski, and D. Chalmers. 2014. “Public reaction to direct-to-consumer online genetic tests: comparing attitudes, trust and intentions across commercial and conventional providers.” Public Understanding of Science: 1-20.

“Direct-to-consumer genetic tests misleading test results are further complicated by deceptive marketing and other questionable practices.” 2010. U.S. Government Accountability Office.

Eriksson, N., et al. 2010. “Web-based, participant-driven studies yield novel genetic associations for common traits.” Public Library of Science Genetics: 6(6).

Farr, C. 2014. “23andMe lands $1.4 million grant from NIH to detect genetic roots for disease.” Reuters, July 29.

“GINA.” 2009. Washington, DC: Department of Health and Human Services.

Gruber, J. 2010. “DTC genetic testing: consumer privacy concerns.”

GeneWatch. Council for Responsible Genetics.

“Hacking Goes Squishy.” 2009. The Economist (US): September 5.

Hogarth, S., G. Javitt, and D. Melzer. 2008. “The current landscape for direct-to-consumer genetic testing: legal, ethical, and policy issues.”

Annual Review of Genomics and Human Genetics 9(1): 161-82.

Hudson, K., et al. 2007. “ASHG statement on direct-to-consumer genetic testing in the United States.” The American Journal of Human Genetics 81(3): 635-37.

Kautz, G. 2010. Direct-To-Consumer Genetic Tests. Washington, DC: United States Government Accountability Office.

Lewis, N. P., et al. 2011. “DTC genetic testing companies fail transparency prescriptions.” New Genetics and Society 30(4): 291-307.

Malin, B., and L. Sweeney. 2001. Re-identification of DNA through an automated linkage process. Journal of the American Medical Informatics Association: 423-427.

McGuire, A. L., C. Diaz, T. Wang, and S. Hilsenbeck. 2009. “Social networkers’ attitudes toward direct-to-consumer personal genome testing. The American Journal of Bioethics 9(6-7): 3-10.

Schleckser, K. 2013. “Physician participation in direct-to-consumer genetic testing: pragmatism or paternalism?” Harvard Journal of Law & Technology 26(2): 696-729.

Seife, C. 2013. “23andMe is terrifying, but not for the reasons the FDA thinks.” Scientific American, November 27.

Singleton, A. et al. 2012. “Informed choice in direct-to-consumer genetic testing (DTCGT) websites: a content analysis of benefits, risks, and limitations.” Journal of Genetic Counseling 21(3): 433-439.

Steck, M. B., and J. A. Eggert. 2011. “The need to be aware and beware of the Genetic Information Nondiscrimination Act.” Clinical Journal of Oncology Nursing 15(3): E34-E41.

Sweeny, L., A. Abu, and J. Winn. 2013. “Identifying participants in the personal genome project by name.” Data Privacy Lab. “Terms and Services.” 2012. 23andMe, accessed May 7, 2014.

Yurkiewicz, S. 2010. “The prospects for personalized medicine.” Hastings Center Report 40(5): 14-16.

About the Author Ameay Naravane is a senior at Georgetown University and candidate for a Bachelor of Science in Foreign Service in Science, Technology, and International Affairs with a concentration in Global Health and Biotechnology.

Dr. Irene Jillson, Assistant Professor in the School of Nursing and Health Studies at Georgetown University, served as the faculty sponsor for this article. Schwartz is also Chair of the Georgetown University Institutional Review Board Social and Behavioral Research Committee.

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Article

Can Recent Neuroimaging Evidence of Consciousness in Vegetative and Minimally Conscious Patients Change our View of Life­-Sustaining Treatments?

Joshua Loewenstern‡ This article serves as a succinct review of recent physiological and imaging findings of patients in vegetative and minimally conscious states demonstrating characteristic patterns of cognitive functional capacities. Researchers have reported recovery of higher-level cognitive function in response to sensory modalities, as well as commandfollowing and communication with the facilitation of neuroimaging technology. The article then discusses the pressing ramifications and questions surrounding life­-supporting treatments for patients in light of the recent findings, including conveying false impressions of hope, implications for diagnosing patients, and maintaining patient autonomy and choice. Relevant ethical concerns and limitations regarding life-­supporting treatments of vegetative and minimally conscious patients are also discussed.

Introduction

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‡ Georgetown University, jnl25@georgetown.edu

A coma is defined as a state of unresponsiveness in which a patient does not exhibit any indication of wakefulness or awareness of the environment. Within about four weeks, patients typically either fully recover, or wake from the coma but remain in a vegetative state known as a minimally conscious state (MCS). Patients diagnosed to be in a vegetative state are seemingly awake but do not show any sign of awareness of the environment or oneself. Patients in an MCS exhibit more signs of wakefulness and inconsistent, but reproducible, indications of awareness of surroundings.

For example, an MCS patient may produce inconsistent but recognizable verbalization that a patient in a vegetative state could not (Monti et al. 2010).

Recent neuroscientific studies have suggested enormous neurological plasticity in patients with severe traumatic brain injury. Patients may retain some cognitive capacities even in the absence of behavioral improvements (Van Der Werf et al.

1999). Over time, patients have exhibited tremendous axon regeneration and have regained neural function in damaged cortices (e.g., Dancause et al. 2005; Sidaros et al. 2008). Such studies provide important knowledge about structural and functional changes in the brain, what patients are able to perceive, and the best treatment options for severe brain-­ injury patients. These studies may offer practical implications for making necessary life or death decisions about artificial life­-supporting treatments. Research investigating capacities

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Imagine that a man is left comatose with a severe head injury after a traffic accident in which his car collided with another vehicle at 80 miles per hour. He requires a ventilator and artificial hydration and nutrition to stay alive. After a few weeks, the man wakes from the coma but is seemingly unaware of his surroundings. Electroencephalography (EEG) reveals patterns of minimal neural activity in response to stimuli. After six months, the patient remains in a vegetative state and doctors believe chances of recovery are very low. At this point, the patient is more likely to remain in a vegetative state than to die or recover. New brain imaging finds that the patient has significantly stronger responses to stimuli, with an uncanny resemblance to normal brain activity. Doctors and the patient’s family are thrilled, but the patient remains immobilized in the hospital.

With new brain imaging demonstrating normal neural activity, does this mean the patient is now aware of his environment? To what extent can we say the patient is “conscious”? Over roughly the last decade, studies investigating patients in vegetative or minimally conscious states have demonstrated evidence of higher-­level processing of sensory stimuli and capacities for cognitive function.

Researchers have found patterns of underlying neural activity resembling that of otherwise healthy and conscious subjects.

Chiefly, what does this mean for the course of treatment for these patients? Can this change our decision on whether to maintain or withdraw life­-sustaining treatments?

Recent Evidence of Consciousness in Vegetative and Minimally Conscious States (MCS)

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for neural activation by sensory tests in recent years has revealed higher-­level cognitive functionality in MCS patients that was not present in vegetative state patients. Larger sample neuroimaging studies found that MCS patients exhibited substantial connectivity among higher-­level cognitive regions for pain perception (Boly et al. 2008) and heightened activation in high-level cortical processing areas for emotional, visual (Zhu et al. 2009) and auditory stimuli (Coleman et al. 2009; Qin et al. 2010). Qin and colleagues even demonstrated activation in the bilateral anterior cingulate cortex, an area associated with self­ -awareness. Somewhat surprisingly, researchers at the University of Cambridge found that a patient in a permanent vegetative state was able to respond to auditory word stimuli. The patient’s recorded brain activation pattern revealed characteristic changes in response to the sounds, indicative of paying attention to the words (Chennu et al. 2013). However, it is still not clear if patients were truly perceiving and comprehending the stimuli.

Research into the communicative abilities of both MCS and vegetative patients has shown that patients in both conditions preserve some capacity for following commands and communication. One study found activation of preparatory premotor areas in vegetative state patients in response to auditory cues to move one hand or the other (Bekinschtein et al. 2011). In other studies, patients who were unable to verbally respond to their healthcare providers were probed to activate supplementary motor areas of cortex by imagining swimming or playing tennis and parahippocampal spatial processing areas by imagining walking through their house (Monti et al. 2010; Owen et al. 2006). A subset of these patients not only successfully showed visible brain activation patterns indistinguishable from otherwise healthy subjects, but one patient was able to answer autobiographical “yes” or “no” questions by putatively invoking motor or spatial imagery. However, follow-­up studies could not confirm consistent communication by this technique (e.g. Bardin et al.

2011). The inconsistent reliability of current neuroimaging technology warrants more research on this mode of interaction that could potentially provide a dependable avenue for patient communication.

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Neuroimaging for PVS/MCS Patients

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Owen et al. (2006) observed similar brain activity on fMRI scans after presenting tennis imagery and spatial navigation imagery to one vegetative patient and a group of 12 healthy control subjects.

Neuroscientists still face challenges in how much therapeutic interventions have been able to help vegetative and MCS patients recover. For instance, Schiff and colleagues (2007) have utilized deep brain stimulation (DBS), a technique that has been somewhat successful in treating patients with Parkinson’s disease and intractable major depression, by implanting electrodes to stimulate activity in thalamo­cortical neural networks which are necessary for input. Following DBS therapy, a patient in an MCS demonstrated a degree of recovery in behavioral responsiveness and was able to interact reliably with family and healthcare providers (Schiff et al. 2007). Additionally, pharmacological interventions using amantadine (Schnakers et al. 2008) or the GABA agonist zolpidem (Clauss & Nel 2006) have shown improvements in both an MCS patient’s motor and cognitive functionality and in temporary arousal from a vegetative state in the respective studies. Thus, research has revealed some hopeful approaches to recovering consciousness and cognitive function, even if just limited to a few patient cases at present.

Treatment Implications While these findings highlight the potential of advancing neurotechnologies in treating certain disorders of consciousness and improving the condition of patients, medical professionals must still confront how such results affect the care of brain­-injured patients. Although the neuroimaging evidence will be helpful to better assess the extent of brain injury and neurological function, the validity of any advancements in neurological testing must be evaluated carefully in order to decide on a course of treatment in each patient’s best interest. Inappropriate use or misinterpretation of results from recent and future neuroimaging studies of MCS or vegetative patients elicits important ethical and treatment implications including: 1) diagnosis of patients, 2) false hope of recovery, and 3) patient choice.

Diagnosis of Patients The recent research of consciousness and brain activity in vegetative or MCS patients has important implications, and possible applications, for the diagnosis of such patients (e.g., Harrison & Connolly 2013). First, uncovering the degree of brain activity may help physicians to make a more accurate diagnosis and prognosis of their brain­-damaged patients, in order to devise the best course of treatment for the patient and his or her family. One recent study had indicated that up to 41 percent of MCS cases were initially misdiagnosed as vegetative states due to the misattributed complexities of their conditions (e.g., Andrews et al. 1996). A battery of tests under electrophysiological recordings or function neuroimaging can assist medical professionals in assessing the degree of damage and the chance of recovery for their patients. The technologies can help classify the degree of damage that can better describe the specific situation of the patient. The imaging techniques can be repeated regularly to evaluate the progress of the patient and help determine any

Neuroimaging for PVS/MCS Patients

False Hope of Recovery

Patient Choice Recent research has produced some results that may have important implications for patient autonomy and choice in the near future. Some of the most exciting studies have revealed that in a few MCS patients, the patient was able to communicate by learning to respond by imagining playing tennis, which activates premotor areas, or walking through his or her home, activating a distinct parahippocampal region (Monti et al. 2010, Owen et al. 2006). This type of interface might provide an avenue for patients in a vegetative or minimally conscious state to communicate with his or her health care professionals and family to regain a degree of autonomy over his or her own health care preferences.

Patients may someday be able to express their level of pain or discomfort to their doctors and live a more comfortable life. Doctors adhering to the principle of nonmaleficence, requiring no harm to be done to the patient, could prevent further distress by providing the patient an avenue to communicate his or her needs. Moreover, when physicians and families are unsure, in the absence of an advance

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In light of recent findings demonstrating the degree of neuronal recovery after severe brain damage, it is easy to overestimate the potential outcome of these patients. Even if patients begin to show close to normal brain activity patterns in response to a battery of stimuli and tests, the patient still remains in a vegetative or minimally conscious state and is unlikely to regain sufficient communicative or cognitive functioning. Cases of reported brain activity recovery in journals and the media can give patients’ families false hope that their loved one will show the same degree of recovery.

It is important that physicians relay to families the reality of the diagnosis that, even with improvements demonstrated by functional brain imaging, it is not likely that their loved one will show complete cognitive recovery. Treatment plans must be made in the best interest of the patient; sustaining

artificial ventilation may reduce the patient’s quality of life to an extent that he may not want to tolerate in exchange for a low likelihood of substantial recovery.

Researchers and physicians are still unsure of what these improvements mean in terms of consciousness and higher­ -level cognition. The studies are the results of early interpretations of ambiguous data. Although neuroimaging data is providing evidence of perception, it still proves challenging for physicians to unequivocally detect consciousness in their patients with the lack of behavioral cues (Giacino et al. 2014). In this way, families may have fallacious misconceptions about the extent of cognitive function the patient has and may have misleading expectations that their loved one may recover far more extensive cognitive and communicative abilities than is likely. Such misconceptions can have potentially profound implications for decisions on life­-supporting treatments (Giacino et al. 2014).

Focusing on anomalous cases of unprecedented recovery, such as Terry Wallis who awoke from an MCS 19 years after a traumatic brain injury, can obscure a family’s decisionmaking when considering whether to sustain life-supporting treatments. Physicians must be honest with families about the severity of a patient’s brain damage and the actual chances of regaining a meaningful level of cognitive function. For instance, decision-making should take into account that new treatments, such as deep brain stimulation and drug therapies, are still experimental in nature and have shown improvements in only a limited number of MCS or vegetative patients. Physicians and families must consider the quality of life the patient will have (e.g., with an intracranial implanted electrode) if the patient only regains minimal functional ability. Thus, in cases of little chance for significant cognitive and behavioral recovery and when life-­supporting therapies are still necessary for many years to come, families must first consider the patient’s future quality of life.

Penn Bioethics Journal

changes in diagnosis or potential outcomes. However, the advancements in technology can also lead to the potential misdiagnoses of patients.

The moral permissibility of whether or not to continue life-­ sustaining treatments is a controversial matter that is both further obscured and particularized with recent advancements in neuroscientific research and rehabilitation efforts. For instance, if a patient is shown to demonstrate brain activity representative of novel cognitive function, the physician may upgrade the diagnosis from a permanent vegetative state to an MCS. Such patients with a high degree of consciousness but who are unable to communicate are said to be in a “locked-in” state. In only limited cases have patients in this state been able to recover significant motor or communicative capacities (Katz et al. 1992). Yet, if the patient demonstrates a degree of awareness or consciousness, some may argue that the family or patient surrogate should elect to continue life-sustaining treatments, as this may be a sign of recovery. On the other hand, if the patient is becoming more aware of his or her incapacitated situation, is this more of a reason to pull the plug? Considering the principle of nonmaleficence, in which one strives to do no harm, physicians and families cognizant of a patient’s capacity to perceive his or her unchanging condition may not believe that continued life support would be in the patient’s best interest in order to avoid a poor quality of life for their loved one.

On a similar note, assessing a patient’s cognitive functioning by neuroimaging techniques may lead to a demotion in diagnosis if the patient does not recover significant brain activity or gets worse. Such a scenario may have immediate treatment implications as a family may be more inclined or even encouraged to remove artificial life-­ sustaining treatments. However, if research later determines that the patient was conscious at the time of removal, this could lead to further family distress and potential legal predicaments. It is important to be aware that diagnostic neuroimaging tools, still imprecise and interpretative, can have grave treatment implications for the patient.

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Neuroimaging for PVS/MCS Patients directive, of the particular ultimate course of treatment the patient would have wanted, there may come a time when the technology is reliable enough for the patient to make a decision about life-­sustaining treatments for him or herself.

Unfortunately, functional brain imaging is too ambiguous and unreliable at its present state to be trusted for unequivocal patient communication (e.g., Harrison & Connolly 2013).

Researchers are not entirely certain that the patients comprehend the tasks or that the brain activation patterns truly represent what they are supposed to show. Therefore, it may be difficult to argue that a patient is well informed and completely competent in their decision­making while in an MCS or vegetative state without explicit communication exchange. It is doubtful that indirect communication through brain imaging will be sufficient enough to make an irreversible legal decision in its current form. However, with further advancements in neuroimaging technology and reliable findings, imaging may be suitable to give minimally conscious patients control over their own life-­supporting treatments in the not-too-­distant future.

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Conclusions As present research continues to uncover signs of conscious processing and neural recovery in vegetative and MCS patients, it is crucial that the medical community consider how the recent evidence will affect healthcare decisions for these patients. Neuroimaging studies have demonstrated exciting higher ­level cognitive processing and potential faculties for communication, but physicians must be cautious not to convey an unrealistic and unfair possibility of recovery to patients’ families. Continued research in this field is very important as the imaging technologies provide vital diagnostic information that can assist physicians and families in understanding the extent of brain injury and making informed decisions about the cessation or continuation of life­-sustaining treatments for each patient. As neuroimaging techniques become more reliable in future years, the evidence of consciousness and potential communication of patient preferences will help medical professionals and ethicists address key issues surrounding a vegetative or MCS patient’s degree of health, quality of life, and best healthcare choices.

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Acknowledgements

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The author would like to first thank Dr. Laura Bishop, Academic Program Officer at the Kennedy Institute of Ethics at Georgetown University for helpful advice and encouragement to pursue this project. The author also thanks Dr. James Giordano from the Pellegrino Center for Clinical Bioethics at the Georgetown University Medical Center for invaluable suggestions and expertise in the field.

References Andrews, K., et al. 1996. “Misdiagnosis of the vegetative state: retrospective study in a rehabilitation unit.” British Medical Journal 313: 13-16.

Bardin, J. C. et al. 2011. “Dissociations between behavioural and functional magnetic resonance imaging-­based evaluations of cognitive function after brain injury.” Brain 134: 769–782.

Bekinschtein, T. A. et al. 2011. “Functional imaging reveals movement preparatory activity in the vegetative state.” Frontiers in Human Neuroscience 5: 5.

Boly, M. et al. 2008. “Consciousness and cerebral baseline activity fluctuations.” Human Brain Mapping 29: 868–874.

Chennu, S. et al. 2013. “Dissociable endogenous and exogenous attention in disorders of consciousness.” NeuroImage: Clinical 3: 450­-461.

Clauss, R. and W. Nel. 2006. “Drug induced arousal from the permanent vegetative state.” NeuroRehabilitation 21: 23­-28.

Coleman, M. et al. 2009. “Towards the routine use of brain imaging to aid the clinical diagnosis of disorders of consciousness.” Brain 132: 2541– 2552.

Dancause, N. et al. 2005. “Extensive cortical rewiring after brain injury.”

Journal of Neuroscience 25(44): 10167­-10179.

Giacino, J. T. et al. 2014. “Disorders of consciousness after acquired brain injury: the state of the science.” Nature Reviews Neurology 14: 99-­114.

Harrison, A. H. and J. F. Connolly. 2013. “Finding a way in: a review and practical evaluation of fMRI and EEG for detection and assessment in disorders of consciousness.” Neuroscience and Biobehavioral Reviews 37: 1403­-1419.

Katz, R. T. et al. 1992. “Long-term survival, prognosis, and life-care planning for 29 patients with chronic locked-in syndrome.” Archives Physical Medicine Rehabilitation 73: 403-408.

Laureys, S. and N. D. Schiff. 2012. “Coma and consciousness: paradigms (re) framed by neuroimaging.” NeuroImage 61: 478-­491.

Monti, M. M. et al. 2010. “Willful modulation of brain activity in disorders of consciousness.” New England Journal of Medicine 362: 579-­589.

Owen, A. M. et al. 2006. “Detecting awareness in the vegetative state.”

Science 313: 1402.

Qin, P. et al. 2010. “Anterior cingulate activity and the self in disorders of consciousness.” Human Brain Mapping 31(12): 1993–2002.

Schiff, N. D. et al. 2007. “Behavioural improvements with thalamic stimulation after severe traumatic brain injury.” Nature 448: 600-­604.

Schnakers, C. et al. 2008. “Measuring the effect of amantadine in chronic anoxic minimally conscious state.” Journal of Neurological and Neurosurgical Psychiatry 79: 225-­227.

Schnakers, C. et al. 2009. “Diagnostic accuracy of the vegetative and minimally conscious state: clinical consensus versus standardized neurobiological assessment.” BioMedCentral Neurology 9: 35.

Sidaros, A. et al. 2008. “Diffusion tensor imaging during recovery from severe traumatic brain injury and relation to clinical outcome: A longitudinal study.” Brain 131(2): 559­-572.

Van Der Werf, Y. D. et al. 1999. “Neuropsychological correlates of a right unilateral lacunar thalamic infarction.” Journal of Neurological and Neurosurgical Psychiatry 66: 36–42.

Zhu, J. et al. 2009. “Cortical activity after emotional visual stimulation in minimally conscious state patients.” Journal of Neurotrauma 26: 677–688.

About the Author Joshua Loewenstern graduated from Georgetown University in 2014 with a Bachelor of Arts in Psychology and a minor in Business Administration.

Dr. Laura Bishop, Head of Academic Programs at the Kennedy Institute of Ethics at Georgetown University, served as the faculty sponsor for this article. Bishop is also the Coordinator for the Dental Ethics Affinity group of the American Society for Bioethics and Humanities.

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