Professional Documents
Culture Documents
Conversations with David Perlman and Jennifer Walter Gun Control and Mental Health Surrogate Motherhood
Also inside:
www.bioethicsjournal.com www.dolphin.upenn.edu/bioethics
Archived editions of the Journal and information about the submission process can be found on our website: http://bioethicsjournal.com The editorial staff also promotes bioethics by hosting campus-wide events through formal lectures, case study presentations, public debates, debriefing of current bioethical issues and student-led conversations. To receive our weekly newsletter, apply to join our editorial staff, or make any inquiries, please email penn.bioethics.society@gmail.com
The Penn Bioethics Journal is published twice a year by the University of Pennsylvania, Philadelphia, PA. All business correspondence, including subscriptions, renewals, and address changes, should be addressed to the Penn Bioethics Journal, 3401 Market Street, Suite 320, Philadelphia, PA 19104. www.bioethicsjournal.com Manuscripts for publication should be submitted according to the submission rules on the website: www.bioethicsjournal.com/submit.html Subscription rates are by request. Permission must be requested for any kind of copying, such as copying for general distribution, advertising or promotional purposes, creating new collective works, or for resale. Requests for these permissions or further information should be addressed to bioethicsjournal@gmail.com Copyright 2013 Penn Bioethics Journal, Philadelphia, PA. ISSN: 2150-5462
Pe n n B i o e t h i c s J o u r n a l
PBJ
EDiTOR IN CHieF Anand Muthusamy PUbLiSHeR Kathleen Sun MaNaGiNG EDiTORS Klyde Breitton Lucy Chen Lili McKinley Ruchita Pendse Sudesh Raju Aditi Verma ASSOciaTe EDiTORS Osama Ahmed Mohammad AlMagweshi Christopher Ataksuka Diana Blidarescu Shayan Cheraghlou Laura Cosgrove Imran Cronk Samantha Freedman Elana Furman Andy Guo Audrey Harnagel Jacquelyn Kemmer Ellen Kim Kurt Koehler Georgio Legerme Nicholas Lim Robin Lo Eileen Mayro Loren Miller Tim Shinn Shashank Sirivolu Hannah Victor Andrew Wadley Abby Worthen Grace Wu Garrett Young Ahmed Yousef Samir Zaman Nikolai Zapertov Timothy Zhou FacULTy ADviSOR Jonathan Moreno, Ph.D.
Contents
Letter from the Editor in Chief
Anand Muthusamy
4 6 7 8 10 11 12 15
Bioethics in Brief
Denmarks Precautionary Approach to Antibiotic Resistance Surrogate Motherhood, Disability, and Abortion in the Case of Baby S Adolescent Organ Donation at the Childrens Hospital of Philadelphia Environmental Applications of Synthetic Biology
Interviews
Adolescent Care and Health Policy A Conversation with Jennifer K. Walter Q&A with David Perlman
Articles
The Potential of Epigenetic Therapy and the Need for Elucidation of Risks
Josh Tycko, Danielle Fields, Daniel Cabrera, Mahamad Charawi, Bradley Kaptur, University of Pennsylvania
17 21 25
Questions or Comments? Please direct all inquiries to the Editor in Chief at bioethicsjournal@gmail.com
Monetary Compensation of Research Subjects: The Shortfalls of Research Standards in Preserving Autonomy
Shivam Amin, University of South Alabama
Bioethics in Brief
Bioethics in Brief
Gun Control and Mental Illness
The results of the Newtown shooting sparked a debate about gun control and mental illness that catalyzed significant political activity. The ethics of gun control and mental health provisions strain a balance between individual privacy and societal safety. Of special concern is the degree to which information about mentally ill patients should be disclosed to prevent dangerous individuals from obtaining firearms. On one hand, patient confidentiality is critical for treatment; however, others argue that a national database is especially useful for firearm regulation. The information required for the database is readily accessible and the number of individuals the system can screen is high (Mowbray 2002). In a world with complete information symmetry, this solution appears to be ideal as suspect individuals can be monitored while others can more freely purchase firearms. However, before the symmetry of information is even considered, the effectiveness of the information must be assessed. First, many individuals already illegally purchase weapons and may be further encouraged to turn to the illegal dealers (Mowbray 2002). Second, increased background checks may only serve to penalize law-abiding gun owners while increasing the cost to the government for perhaps a marginally effective system (Kapur 2013). Third, those who voluntarily seek treatment are most likely not the ones interested in purchasing firearms for an ulterior motive (Swanson 2013). These three points not only question the meaningfulness of a database but also warrant a discussion of unintended side effects in collecting information. Disclosure of personal information further exposes patients to stigma, which may hinder them from seeking mental healthcare. The increase in untreated mental illnesses not only adversely affects patients, but also may result in increased criminal activity. Jeffrey Swanson, a professor of psychiatry and behavioral sciences at Duke University, studied the correlation between policy action and subsequent criminal behavior of the mentally ill (Webster 2013). Swanson considered two groups: the mentally ill with a criminal history and the mentally ill without one. When aggregating both of these groups, policy appeared to have no significant effect on decreasing violent crimes by the mentally ill as a whole (Webster 2013). However, analyzing the two separate groups individually yielded more decisive results. Regulation did decrease the risk of future violence for patients without criminal records. However, for those with criminal records, the more restrictive gun control policy, surprisingly, increased the likelihood of future violent crimes by a staggering 60 percent (Webster 2013). Swanson suggests that increased stigma and stronger regulations affect the individuals desire to reach out for medical attention when under scrutiny. Specifically, patients with criminal history especially feel judged and persecuted, thinking that they have more to lose or hide. Without that patient-doctor confidentiality, these patients are less likely to trust in a medical institution that appears to have not just their interest but also societys interest at heart (Mowbray 2002). Therefore, while it is critical to have some form of background check or regulation in society, the intent should be on helping and reducing the number of mentally ill, rather than solely focusing on preventing people from obtaining weapons (Webster 2013).
Dean Rohrer
The Obama administrations recent proposals regarding gun control and mental health care represent societys next steps. Specifically, the administration seeks 23 stipulations that converge in two specific executive orders: the first closes loopholes in the current background check system and the second keeps surplus military weapons off the streets (White House 2013). The Obama administration plans to target mental illness by allocating $235 million in the 2014 fiscal budget proposal to three distinct areas: training for teachers in public schools, education for medical physicians, and alleviation for schools with violent history (Kliff 2013). The overlap of the two proposals provides a focus and sense of priority in the nation to address mental health concerns. However, while the gun control proposals and mental health budget are steps forward, the most critical component of all these stipulations remains understated: the need for enforcement, which brings with it the power of suspicion
Bioethics in Brief
(Devers 2013). Implementing policy necessitates training and heightened awareness, which reinforces strong stereotypes (Link 1999). The stigma of the mentally ill and the stigma of criminals permeate through society as individuals attempt to carry out the very laws that try to resolve this ingrained stereotype. Ultimately, people need to bring the best interests of others to the forefront and communicate a desire to genuinely help. By demonstrating this true interest in the success of the involved individuals, the issue of gun control and mental illness in society may finally begin to resolve itself (Corrigan 2002). -Aditi Verma, University of Pennsylvania
Corrigan, P. W., Rowan, D., Green, A., Lundin, R., River, P., UphoffWasowski, K., et al. 2002. Challenging two mental illness stigmas: personal responsibility and dangerousness. Schizophrenia Bulletin. 28(2), 293309. Devers, C. E., T. Dewett, Y. Mishina, and C. A. Belsito. 2013. A General Theory of Organizational Stigma. Organization Science 20(1): 154-171. Kliff, Sarah. 2013. Obamas Proposed Budget to Seek $235 Million for New Mental Health Programs. Washington Post. N.p. Link, B. G., J. C. Phelan, M. Bresnahan, A. Stueve, and B. A. Pescosolido. 1999. Public Conceptions of Mental Illness: Labels, Causes, Dangerousness, and Social Distance. American Journal of Public Health 89(9): 1328-1333. Mohney, Gillian. 2013. Obama Budget Includes $235 Million For Mental Health Care. ABC News. ABC News Network, Moorhead, Molly. 2013. A Summary of the Manchin-Toomey Gun Proposal. PolitiFact. Tampa Bay Times. Mowbray, Carol T. 2002 Mental Health and Mental Illness: Out of the Closet? Social Service Review 75.1 135-79. Print. Obama Announces 23 Executive Actions, Asks Congress to Pass Gun Laws. 2013. Web log post. CNN. CNN News. Swanson, Jeffrey, PhD. 2013. Mental Illness and New Gun Law Reforms: The Promise and Peril of Crisis-Driven Policy. The Journal of American Medical Association 309(12): 1233-1234. The White House, Office of Press Secretary 2013. FACT SHEET: New Executive Actions to Reduce Gun Violence. The White House. The White House. 2013. Now Is the Time. Rep. The White House. Webster, Daniel W., and Jon S. Vernick. 2013. Reducing Gun Violence in America Informing Policy with Evidence and Analysis. Baltimore: Johns Hopkins UP. Wilkie, Christina. 2013. NRA: Background Check Deal A Positive Development, But Still Oppose Compromise Plan. The Huffington Post. TheHuffingtonPost.com.
Bioethics in Brief
ahead of the evolution of antibiotic strains. The Office of the Chief Scientists of Australia released a paper that urged scientists to develop more effective antibiotics and vaccines to fight growing antibiotic resistance in bacteria (Prasad and Smith 2013). In the United States, there are also new movements. U.S. Representative Louise Slaughter (D-NY) wrote to Nature in August 2013 that she has been striving to pass legislation to ban the use of eight medically important classes of antibiotics currently used in agriculture. Her piece was in response to several articles published in Nature: MRSA: Farming up Trouble, Antibiotic Resistance: The last resort, and Antibiotic Threat (Slaughter 2013). Supplementing Representative Slaughters concern that treating livestock with antibiotics increases humans risk of acquiring an antibiotic resistant infection is a new study released by Johns Hopkins University that used data from a major health system, the Geisinger Health System. This study showed that exposure to swine manure, which contains antibiotic resistant bacteria, resistance genes, and antibiotics, increases an individuals risk of contracting MRSA (Casey 2013). Especially as we see growing evidence of antibiotic resistance, it is time the United States takes action to reduce resistance in our own country. Despite worries of limited antibiotic use leading to decreased animal quality of life, the evidence supports that banning antibiotics for use in agriculture reduces the possibility of infectious bacteria evolving into something more dangerous. Antibiotics still are magic bullets for specific ailments, and in order to protect their effectiveness, we must both carefully use and continually develop drugs to outpace the development of resistance. -Lilian McKinley, University of Pennsylvania
Aarestrup, F.M., A.M. Seyfarth, H. Emborg, K. Perdersen, R.S. Hendriksen, F. Bager. 2001. Effect of Abolishment of the Use of Antimicrobial Agents for Growth Promotion on Occurrence of Antimicrobial Resistance in Fecal Enterococci from Food Animals in Denmark. Antimicrobial Agents and Chemotherapy 45(7): 2054-2059. Casewell, Mark, et. al. 2003. The European ban on growth-promoting antibiotics and emerging consequences for human and animal health. Journal of Antimicrobial Chemotherapy (52): 159-161. Casey, John, et. al. 2013. High-Density Livestock Operations, Crop Field Application of Manure, and Risk of Community-Associated Methicillin-Resistant Staphylococcus aureus Infection in Pennsylvania. JAMA Internal Medicine. E1-E11. Chan, Margaret. 2012. Antimicrobial Resistance in the European Union and the World. WHO. Forslund, Kristoffer, S. Sunagawa, J.R. Kultima, D. Mende, M. Arumugam, A. Typas, P. Bork. 2013. Country-specific antibiotic use practices impact the human gut resistome. Genome Research (23): 1163-1169. Prasad, Simon and Phillipa Smith. 2013. Meeting the Threat of Antibiotic Resistance: Building a New Frontiline Defense. Occasional Paper Series (7): 1-4. Slaughter, Louise. 2013. Antibiotics: Support US policy change. Nature 500: 400. Wharam, Barney and L. Lazarou. 2013. Ethical considerations in an era of mass drug administration. Parasites and Vectors 6(1): 234.
Bioethics in Brief
possible children. Parents should support selection against disability whenever selection is possible and better outcomes likely exist. The principle argues that [the] reason to select the child with better prospects is that the child [is likely to] benefit more than the other would by being caused to exist (2009). According to PB, Kelley should have accepted abortion and helped the couple conceive another child without expected disabilities. However, the case of Baby S involves some issues not considered by Savulescu and Kahane, such as monetary concerns and legal issues in kidnapping Baby S. Furthermore, PB overall does not consider the societal implications of its directivesnamely, that only those with the education and resources to consider selective abortion can do so. PB provides a highly relevant framework to inform choices in selective abortion of the disabled, but it is not complete in assessing this case. The case of Baby S provides a good example of bioethics being applied to a real situation with real consequences. This case also illustrates that few real life situations are as simple as the assumptions employed by PB. The case of Baby S demonstrates that we cannot just consider core issues of an ethical dilemma one at a timethey are all intertwined. That said, frameworks such as PB are still essential to making informed decisions. Just as this system informs the ethics of selective abortion, others consider the monetary, legal, and societal implications. As bioethics grows as a field, we may expect to see future frameworks that take all such matters into consideration so that future medical decisions may have more comprehensive ethical guidance in situations such as the case of Baby S. -Klyde Breitton, University of Pennsylvania
Anderson, E.S. 2000. Why Commercial Surrogate Motherhood Unethically Commodifies Women and Children: Reply to McLachlan and Swales. Health Care Analysis 8: 19-26. Cohen, E. 2013. Surrogate offered $10,000 to abort baby. CNN. Available at http://www.cnn.com/2013/03/04/health/surrogacy-kelley-legalbattle/index.html?iref=allsearch. Savulescu, J. and Kahane, G. 2009. The Moral Obligation to Create Children with the Best Chance of the Best Life. Bioethics 23(5): 274290.
Bioethics in Brief
Bioethics in Brief
the possibility that animals affected by genetic modification may be harmed. For example, the insertion of the fungal resistance gene in the R. silius frogs could have unforeseen negative consequences for the frogs themselves and for other organisms that interact with them, especially their predators. While remaining wary of these concerns and others that were discussed, biologists, environmentalists, and ethicists alike are optimistic about the potential for synthetic biology to make meaningfuland safecontributions to the field of environmental science. -Ruchita Pendse, University of Pennsylvania
Callaway, Ewen. 2013. Synthetic biologists and conservationists open talks. Nature 496: 281. Sanderson, Katharine. Synthetic biology gets ethical. Nature. 12 May 2009. Web. <http://www.nature.com/news/2009/090512/full/ news.2009.464.html> United States. Presidential Commission for the Study of Bioethical Issues. Synthetic Biology. 2010. Web. <http://bioethics.gov/taxonomy/term/1>.
Interview
PBJ: Why are goals of care conversations important in providing good care? JKW: When a child has a serious or chronic illness, data from parents demonstrate that they want honest, timely information about their childs condition3,4 and want to participate in choosing between different treatment options. These conversations discuss what goals or hopes parents have for their child and how they would like to prioritize different care options. Only by engaging families in these discussions about what they value most can we as health care providers offer truly family centered care. In fact, the American College of Critical Care Medicine recommends that these kinds of conversations happen with patients and families within 24-72 hours of patients being admitted to intensive care units.5 PBJ: How do you assess the quality of these conversations? JKW: There is a whole body of research that assesses the quality of communication in healthcare and quantifies everything from the amount of time that different members of a conversation speak, the number of empathetic statements used, and even different aspects of nonverbal communication. Most of this research relies upon at least audio taping of conversations (or video taping in cases that assess nonverbal communication) and a standardized scoring system that is applied to the interaction.6,7 PBJ: What are some of the barriers for providers that prevent them from engaging families in goals of care conversations? JKW: In the interviews Ive done with pediatric oncologists and intensive care doctors, they describe several barriers to having frank conversations with patients and families about prognosis and goals of care. First, often there is significant medical uncertainty, and providers do not want to be inaccurate about a bad prognosis and
Healthcare Policy
PBJ: How would the concept of equality function in healthcare policy? JKW: In terms of healthcare policy, equality refers to a reduction in the disparities of health outcomes and kinds of care offered to different classes of patients. There is significant evidence that there are health disparities based on race, gender and class in the US.9,10 Many theories of justice defend an equality of opportunity, which would include access to health care that treats all like patients alike, regardless of race, class, gender or education. PBJ: How does ACA ignore discussions of equality? JKW: The ACA, while doing many important things to expand access to health care to millions of Americans who are currently uninsured, has largely focused on improving the quality of care, while not emphasizing the importance of ensuring that all Americans receive similarly high quality care. In our article, we argued that this approach of ensuring equality-in-quality will improve health in important ways. Empirical evidence for this approach can be found in vaccine policies that worked to prioritize improving vaccination rates among impoverished children and thereby reducing the disparity in vaccination by this group, which lead to improved immunity for the entire community.11
Professional Experience
PBJ: Please explain your academic trajectory. How did your interests in philosophy develop and lead to medicine? JKW: I have wanted to be a physician since I was about 7 years old, but when I started college my parents encouraged me to major in whatever I enjoyed, since I could complete my premed requirements at the same time. I fell in love with philosophy and the way it taught me to critically think about many different aspects of life. I thought my training in philosophy would end when I started medical school, but then I learned about the program at Georgetown that paired both a PhD in Philosophy with a medical degree. I dont believe the program still exists, but Edmund Pellegrino, who started the program, was a visionary in recognizing that clinicians who were bioethicists have a unique understanding of bioethical challenges and the potential solutions to those dilemmas. PBJ: How does your knowledge of philosophy, and bioethics in particular, inform your day-to-day practice as a physician? JKW: Because of my training in philosophy, I developed the ability to recognize how individual behaviors or institutional policies perhaps could have a larger impact on how we as health care providers fulfilled our ethical obligations to care for patients. For example, I realized that when physicians avoided the difficult conversations with families and patients
13
References
1. Ross L. Children, families and health care decision-making. New York: Oxford University Press; 1998. 2. Walter JK. Supporting Her Autonomy: The Obligations of Guardians and Physicians in Adolescents Refusals of Care. Journal of Clinical Ethics. 2012;23(1):56-59. 3. Shudy M, de Almeida M, Ly S, et al. Impact of pediatric critical illness and injury on families; a systematic literature review. Pediatrics. 2006;118(S3):S203-219. 4. Meert KL, Eggly S, Pollack M, et al. Parents perspectives on physician-parent communication near the time of a childs death in the pediatric intensive care unit. Pediatr Crit Care Med. Jan 2008;9(1):2-7. 5. Davidson J, Powers K, Hedayat K, et al. Clinical practice guidelines for support of the family in the patient-centered intensive care unit: American College of Critical Care Medicine Task Force 2004-2005. Crit Care Med. 2007;35(2):605-622. 6. Curtis J, Engelberg R. Measuring success of interventions to improve the quality of end-of-life care in the intensive care unit. Critical care medicine. 2006;34(11 Suppl):S341-347. 7. Roter DL, Stewart M, Putnam SM, Lipkin M, Jr., Stiles W, Inui TS. Communication patterns of primary care physicians. JAMA : the journal of the American Medical Association. Jan 22-29 1997;277(4):350-356. 8. Walter JK, Rosenberg A, Feudtner C. Tackling taboo topics: how to have effective advanced care planning discussions with adolescents and young adults with cancer. JAMA Pediatrics. 2013;11:1-3. 9. 2010 National Healthcare Disparities Report. Rockville, MD: Agency for Healthcare Research and Quality;2011. 11-0005. 10. Medicine Io. Toward Health Equity and Patient-Centeredness: Integrating Health Literacy, Disparities Reduction, and Quality Improvement: Workshop Summary. Disparities Reduction, and Quality Improvement: Workshop Summary 2009. 11. Davis MM, Walter JK. Equality-in-Quality in the Era of the Affordable Care Act. JAMA. 2011;306(8):872-873. 12. Goold SD, Biddle AK, Klipp G, Hall CN, Danis M. Choosing Healthplans All Together: A Deliberative Exercise for Allocating Limited Health Care Resources. Journal of Health Politics, Policy and Law. 2005;30(4):563-602.
Interview
PBJ: Would that also be interactive? DP: Im hoping people would be able to do it via their cell phones or clickers. Ive thought about the novel and turning it into a screenplay, and I have people Id love to play certain parts. For the Latino woman who gets a transplant, Id love to have Jessica Alba because I really liked her in the series Dark Angel. For the black male surgeon, Id like Will Smith because hes a homeboy from West Philadelphia. PBJ: What do you want readers to learn from the choices they make in the interactive novel? DP: The feedback that Ive had from readers is that what theyll do is sit down first and use their gut instinct, but then theyll go back and explore the various options, so its almost like getting 15 books in one. I hope that when they make those choices, theyre also reflecting on why a character might choose that. But its also designed as a page-turner.
Article
The Potential of Epigenetic Therapy and the Need for Elucidation of Risks
Josh Tycko, Danielle Fields, Daniel Cabrera, Mahamad Charawi, Bradley Kaptur
Epigenetic phenomena are known to be a root cause of many common diseases. To date, the FDA has approved four epigenetic therapies that show promising results for prolonging lives of terminal cancer patients. However, there is a relative lack of knowledge about long-term epigenetic effects, especially those that affect future generations. We propose a heightening of standards for epigenetic therapy: therapies should be targeted to specific genes in specific cells and cannot affect the germline and patients epigenomes should be sequenced before and after treatment. Moreover, further research should be performed to answer questions about transgenerational epigenetic effects, to analyze the effects of altered epigenomes in the long term, and to develop superior assays for screening epigenomes. We highlight current research in the field, including the work of the Penn iGEM group.
Epigenetics Background
Introduction. The code of life is more than a sequence of As, Cs, Ts, and Gs. Muscle cells in the human heart contain the same DNA as skin cells in the foot, yet these two cell types behave in radically different ways. Both contain the DNA for over 20,000 human genes but express only the ones needed for their own form and function. These differences in gene expression are modulated by epigenetic controls. Epigenetics refers to any heritable chemical modification of DNA that alters expression without changing genetic sequence. Neurodevelopmental disorders, immunodeficiency, cancer, and other illnesses can result when these mechanisms go awry. Methylation. In humans, enzymes called methyltransferases add methyl groups to short DNA sequences, called CpG sites, abundant in the genome. Methyl groups block transcription factors (gene activators) from binding to DNA and performing their normal function. Although epigenetic factors do not change the sequence of DNA, they can affect the phenotype, the observable characteristics of the organism. Specific patterns of methylation are necessary for a cell to modulate the level of expression of each of its genes.
one of the leading genetic causes of intellectual disability, is characterized by hypermethylation, which disrupts the production of protein necessary for normal brain development. Patients suffering from this disorder are at risk for autism, ADHD, decreased IQ, infertility in females, and distorted facial features ( Jacquemont 2011). Psychological. Epigenetic mechanisms can also impact psychological states. In an animal study, rat pups that received better maternal care in the form of licking, grooming, and arched-back nursing had lower levels of methylation at the glucocorticoid receptor gene. These rats displayed less intense responses to stressful situations than those who received poor maternal care. The researchers were able to eliminate these differences via epigenetic interference (Weaver 2004).
Epigenetic Therapy
Epigenetic Diseases
Cancer. DNA methylation has been referred to as the hallmark of cancer (Szyf 2004). Abnormal methylation patterns throughout the genome that cause blockage of tumor suppressor genes have been linked to many types of cancer. For instance, breast cancer generally exhibits inactivation of the gene BRCA1. In sporadic (i.e. non-familial) cases, this suppression is usually caused by hypermethylation rather than mutation of the gene (Rice 2000). In other cases, hypomethylation causes overexpression of the flap endonuclease 1 gene and lead to breast cancer in some patients (Singh 2008). Neurological. Methylation abnormalities have been linked to a wide range of diseases. Fragile X syndrome,
University of Pennsylvania, Penn iGEM 2013
Fundamental Advantages. The aforementioned epigenetic roots of disease are attractive targets for therapy. Aberrant DNA methylation patterns are more easily reversible than genetic mutations. In the case of cancer, epigenetic therapy coaxes tumor cells to return to a healthy state, rewiring their methylation patterns so the cells express genes that halt their cancerous uncontrolled growth. Traditional chemotherapy strategies, on the other hand, aim to kill cancer cells and are fundamentally more toxic to patients since healthy cells are also harmed. Recent Successes. There have been some exciting clinical successes with the first generation of epigenetic therapies. To date, four epigenetics treatments have been approved by the FDA for use in cancer patients: Zolinza, Istodax, Vidaza, and Dacogen (Claus 2005). The first two are histone deacetylase inhibitors and prevent histone modifications, a type of epigenetic change; the second two inhibit DNA methylation. These compounds are chemical analogues of the DNA base cytosine (C), and at low doses, they bind to the methyltransferases so that they dont come into contact with the patients actual DNA, preventing the DNAs methylation. At high doses, they
The Potential of Epigenetic Therapy and the Need for Elucidation of Risks
can incorporate into the DNA or RNA itself and reduce cell viability. These treatments are used, at low doses, to reverse hypermethylation in patients with myelodysplastics syndromes (MDS), a spectrum of blood cell disorders that can lead to anemia and heighted susceptibility to infections. The drugs effectively reverse cancerous hypermethylation and return standard function to cell-cycle genes, restoring normal growth rates. However, fewer than 10 percent of patients experience a complete response, a total reversal from diseased to healthy bone marrow and blood (Silverman 2002). Problems. The results of first generation epigenetic therapies are promising, but these drugs should not be seen as the ideal model for future developing therapies, especially if doctors want to treat younger patients with non-lethal epigenetic diseases. First generation drugs fail to satisfactorily address many issues. For one, they all inhibit DNA methylation processes. As previously mentioned, many cancers can be caused by low methylation levels, and would need to be treated with drugs that restore normal methylation levels (Feinberg 2004). Second, the current drugs work by blindly affecting all genes in the genome of all the cells they encounter. One of the scientists behind the Dacogen studies noted there is a potential for harm, but so far the adverse events, including red blood cell suppression, diarrhea, anorexia, and others, have been deemed acceptable by the FDA (Issa 2007). It is possible that the potential for greater harm will be realized if epigenetic therapies are used on patients with a much longer expected life span than the current patient population. need to push new drugs and ensure safe use. Methylationsensitive genome sequencing in multiple cell types for each patient would reveal potential off-target effects. This kind of personalized medicine could obviate the need of a longitudinal clinical trial. This is difficult and expensive with existing technologies, and these procedural problems must be overcome so that adequate assessment of epigenetic therapies can be performed (Laird 2010). As more research is conducted, the balance between clinical trials and personal diagnostic tests and the responsibilities of those involved must be considered. Trans-generational Risk. The issues discussed thus far are not unique to first generation epigenetic therapies. They act blindly not only on a genomic level, but also in terms of affected cell type. We cannot exclude the possibility that these treatments will affect the epigenomes of germline cells. In fact, recent studies demonstrate that Dacogen could interfere with embryo implantation and harm the fetus if given to a pregnant woman or to a man or woman planning on having children (Ding 2012). There is evidence that epigenetic modifications can be inherited by children and even grandchildren, so doctors need to keep the health of future generations in mind (Grossniklaus 2013). The effect of epigenetic therapies on germline cells should be measured not only while the drug is being administered, but also in follow-ups after the treatment is finished. It is critical that more basic research is performed to determine the extent of transgenerational epigenetic effects. If we acknowledge that some patients will have children regardless of any warnings, we must consider if it is acceptable to have synthetically altered epigenomes in the population.
Ethical Questions
18
Long Term Risk. Research has not yet fully elucidated the effects of DNA methylation (Rothstein 2009). Therapies may have off-target effects that are difficult to observe especially if they appear years after the initial therapy. To date, approved trials have been conducted with very sick, elderly cancer patients, but research has confirmed epigenetic modifications can affect us on a longer, even transgenerational, time-scale (Rothstein 2009). Clinical trials however do not normally track side-effects ten, twenty, or thirty years after treatment. If these treatments alleviate disease in the short term but eventually cause unforeseeable epigenetic abnormalities, are they acceptable for younger patients with non-terminal diseases? Most would argue this depends on the gravity of the adverse effectsa risk/ benefit analysis similar to that performed for any drug approval should be conducted. Therefore, clinical trials must be designed to take these risks into account. Trials and follow-ups should last for a sufficient amount of time to assess these risks on the decade time scale. On the other hand, if the drug does show an immediate benefit in the trial subjects, the ethics of delaying its medical use until the conclusion of the trial must be assessed. Certainly, trials of such durations with these looming questions would be unfavorable for the pharmaceutical investment community. Comprehensive diagnostic tests could help balance the
18 18
The Potential of Epigenetic Therapy and the Need for Elucidation of Risks
technology to enable the promise of personalized epigenetic treatment. Research at Penn and Beyond. These more stringent safety standards demand the development of secondgeneration epigenetic therapeutics that are properly targeted at the genomic and cellular levels. In the past few months, we have seen promising initial published work on new tools for manipulating the genome in a careful, targeted manner. Histone methylases, histone demethylases, and DNA demethylases have all been engineered to act on specific DNA sequences (Konermann 2013, Mendenhall 2013, Maedner 2013). Our research team at the University of Pennsylvania, Penn iGEM, took initial steps to complete this suite of tools by designing a novel enzyme that selectively restores methylation at specific DNA sites. More importantly, we have developed an alternative DNA methylation assay, called MaGellin, which is significantly simpler, faster, and cheaper than methylation-sensitive sequencing for applications like ours to accelerate the optimization of these tools. These efforts would not have been possible without the expert advice of the University of Pennsylvanias epigenetics research labs. Dr. Marisa Bartolomeis lab is actively studying how methylation patterns are transmitted across generations. Additionally, Dr. Rebecca Simmons lab in the Perelman School of Medicine has discovered a way to reverse epigenetic modifications including DNA methylation and prevent the onset of obesity in a rat model. Conclusion. Epigenetic phenomena have a significant impact on the way we live and grow and can be responsible for the way we die. The need for epigenetic therapies is clear and the initial successes are promising for cancer patients, but the model for future developments is not yet set in stone. If doctors want to treat younger patients with non-lethal epigenetic diseases, the consideration of risks must include the long term, and the decisions in the clinic must be based on data from researchers asking fundamental questions. The proposed second generation epigenetic therapies could overcome the hurdles of restoring methylation, as opposed to only inhibiting methylation, and targeting specific genes as opposed to the entire genome. However, the issues of their delivery and cellular targeting still loom. While it will require significant effort from basic researchers to determine the relevant mechanisms to optimize the clinical strategies, the path forward is promising.
References
Campion, J., Milagro, F., & Martinez, J. A. 2010. Epigenetics and obesity. Progress in Molecular Biology Translational Science 94: 291347. Claus, R., Almstedt, M., & Lubbert, M. 2005. Epigenetic treatment of hematopoietic malignancies: in vivo targets of demethylating agents. Seminars in Oncology 32(5): 511-520. Ding, Y. B., Long, C. L., Liu, X. Q., Chen, X. M., Guo, L. R., Xia, Y. Y., et al. (2012). 5-aza-2-deoxycytidine leads to reduced embryo implantation and reduced expression of DNA methyltransferases and essential endometrial genes. PLoS One 7(9): e45364. Feinberg, A. P., & Tycko, B. 2004. The history of cancer epigenetics. Nature Reviews Cancer 4(2): 143-153. Grossniklaus, U., Kelly, B., Ferguson-Smith, A. C., Pembrey, M., & Lindquist, S. 2013. Transgenerational epigenetic inheritance: how important is it? Nature Reviews Genetics 14(3): 228-235. Issa, Jean-Pierre. Interview by Nova. Nova. Public Broadcasting System. October 16, 2007. Jacquemont, S., Curie, A., des Portes, V., Torrioli, M. G., Berry-Kravis, E., Hagerman, R. J., et al. 2011. Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Science Translational Medicine 3(64): 64ra61. Kerkel, K., Schupf, N., Hatta, K., Pang, D., Salas, M., Kratz, A., et al. 2010. Altered DNA methylation in leukocytes with trisomy 21. PLoS Genetics 6(11): e1001212. Kondo, T., Bobek, M. P., Kuick, R., Lamb, B., Zhu, X., Narayan, A., et al. 2000. Whole-genome methylation scan in ICF syndrome: hypomethylation of non-satellite DNA repeats D4Z4 and NBL2. Human Molecular Genetics 9(4): 597-604. Konermann S, Brigham MD, Trevino AE, Hsu PD, Heidenreich M, Cong L, Platt RJ, Scott DA, Church GM, Zhang F. 2013. Optical control of mammalian endogenous transcription and epigenetic states. Nature 500(7436): 472-6. Laird, P. W. 2010. Principles and challenges of genomewide DNA methylation analysis. Nature Review Genetics 11(3): 191-203. Maeder ML, Angstman JF, Richardson ME, Linder SJ, Cascio VM, Tsai SQ, Ho QH, Sander JD, Reyon D, Bernstein BE, Costello JF, Wilkinson MF, Joung JK. 2013. Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins. Nature Biotechnology. Online publication ahead of print. Mendenhall EM, Williamson KE, Reyon D, Zou JY, Ram O, Joung JK, Bernstein BE. 2013. Locus-specific editing of histone modifications at endogenous enhancers. Nature Biotechnology. Online publication ahead of print. Rice, J. C., Ozcelik, H., Maxeiner, P., Andrulis, I., & Futscher, B. W. 2000. Methylation of the BRCA1 promoter is associated with decreased BRCA1 mRNA levels in clinical breast cancer specimens. Carcinogenesis 21(9): 1761-1765. Rothstein, M. A., Cai, Y., & Marchant, G. E. 2009. The ghost in our genes: legal and ethical implications of epigenetics. Health Matrix 19(1): 1-62. Silverman, L. R., Demakos, E. P., Peterson, B. L., Kornblith, A. B., Holland, J. C., Odchimar-Reissig, R., et al. 2002. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. Journal of Clinical Oncology 20(10): 2429-2440. Singh, P., Yang, M., Dai, H., Yu, D., Huang, Q., Tan, W., et al. 2008. Overexpression and hypomethylation of flap endonuclease 1 gene in breast and other cancers. Molecular Cancer Research 6(11): 17101717. Szyf, M., Pakneshan, P., & Rabbani, S. A. 2004. DNA methylation and breast cancer. Biochemical Pharmacology 68(6): 1187-1197. U.S. Food and Drug Administration. Cellular and Gene Therapy Guidances. Last modified July 2, 2013. http:// www.fda.gov/BiologicsBloodVaccines/GuidanceCompliance RegulatoryInformation/Guidances/CellularandGeneTherapy/ default.htm. Weaver, I. C., Cervoni, N., Champagne, F. A., DAlessio, A. C., Sharma, S., Seckl, J. R., et al. 2004. Epigenetic programming by maternal behavior. Nature Neuroscience 7(8): 847-854.
Penn iGEM is an undergraduate research team that only exists because of the generous support of many individuals and companies (see http://2013.igem. org/Team:Penn). Dr. Brian Chow of Penn Bioengineering advises and directs the team. Dr. Jordan Miller of Bioengineering at Rice University also advises the team. Spencer Glantz, Mike Magarici, Avin Veerakumar, and Dr. Orkan Telhan have also provided invaluable expertise. Drs. Brian Chow, Benjamin Tycko, and Marisa Bartolomei reviewed and provided comments on this manuscript.
The Scattergood Program for the Applied Ethics of Behavioral Healthcare is dedicated to applied research and scholarship in all areas of behavioral healthcare ethics. Housed at the University of Pennsylvania, in the Department of Medical Ethics & Health Policy, the ScattergoodEthics Program is a regional and national effort that welcomes all those active in the field of behavioral healthcare.
Bioethics
M.A. IN BIOETHICS
www.bioethics.as.nyu.edu/page/discover
New York University is an afrmative action/equal opportunity institution.
20
Article
Shivam Amin
Monetary Compensation of Research Subjects: The Shortfalls of Research Standards in Preserving Autonomy
Biomedical researchers are expected to respect the autonomy of human subjects through the process of informed consent. The Belmont Report established the principle of respect for autonomy as a cornerstone of biomedical research ethics in 1979. However, researchers can find it difficult to uphold this ideal when compensating human subjects. Ambiguities in both the Belmont Report and government guidelines complicate pinpointing exactly how to preserve the autonomy of research subjects. The process of informed consent itself poses a set of problems for researchers. Specifically, the term undue inducement, describing a concept central to the preservation of a subjects autonomy, is particularly vague and warrants further investigation. It is certainly possible that researchers can undermine a subjects autonomy through the offer of a monetary payment. However, the magnitude of this problem is nearly impossible to measure because inconsistencies in policy make it extremely difficult for researchers to respect the principle of respect for autonomy in practice. Once some of these inconsistencies are resolved, researchers can then explore the underlying so-
Introduction
Respect for autonomy is one of the cornerstone principles of bioethics. According to Tom Beauchamp and LeRoy Walters, two leading bioethicists at the Kennedy Institute of Ethics, personal autonomy refers to personal self-governance: personal rule of the self by adequate understanding while remaining free from controlling interferences by others and from personal limitations that prevent choice (2003). The idea that one should respect another persons right to decide his or her own fate is largely a product of Western culture and has become deeply ingrained in biomedical research ethics. The principle of autonomy is rooted in the Kantian conception of human beings as ends in themselves and never only as means to an end ( Johnson 2012). This paper explores the principle of respect for autonomy as it relates to the practice of monetarily compensating human research subjects.
In the United States, in 1979 the Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, Report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, hereafter the Belmont Report, helped establish an ethical framework for biomedical research involving human subjects. While the Report has no legal enforcement mechanism, the scientific community has embraced the Reports guidelines to help resolve potential ethical dilemmas. The Belmont Reports principles also guide institutional review boards (IRBs) and executive bodies in the US that oversee most research projects involving human subjects. IRBs are usually
affiliated with academic institutions and consist of at least five professionals of varying backgrounds. These individuals have the authority to approve or reject any research project in which human subjects are involved (DHHS 1993). Each major institution conducting human subject research will have at least one such IRB panel that must approve any proposal of such research. The Belmont Report highlights three ethical principles that serve as the moral backbones for biomedical research ethics: respect for persons, beneficence, and justice (HEW 1979). Central to the principle of respect for persons is the notion that every person be treated as an autonomous individual. According to the Belmont Report, an autonomous individual is someone who is capable of making personal decisions through careful deliberation. To respect autonomy is to not obstruct this decision-making process. The Belmont Report underscores the importance of informed consent as a way to ensure respect for autonomy. In order to provide informed consent, a potential human research subject should be made aware of what a research project entails and be afforded the right to choose whether or not to participate in the project. Informed consent is contingent upon three factors: information, comprehension, and voluntariness. A potential research subject must be given a thorough overview of a research project in an understandable manner. Ultimately, the subject must use this understanding to voluntarily give consent to participate in the project (HEW 1979). When voluntarily giving consent, an individual must be free of coercion or undue influence (HEW 1979). The Belmont Report states that undue influence occurs through an offer of an excessive, unwarranted, inappropriate
21
22
Perversion of Choice
Coercion and undue inducement are two ways researchers can potentially undermine autonomy. Because blatant coercion involves an actual threat towards a research subject, it is unlikely that a subject will ever feel threatened to participate in a research project as long as IRBs are intact (HEW 1979). However, the problem of undue influence is very real and needs to be addressed. Although there is no general consensus on what undue influence entails, Ezekiel Emanuel, an acclaimed bioethicist at the University of Pennsylvania, highlights four factors that create undue influence: 1. An Offered GoodIndividuals are offered something that is valuable or desirable in order to do something. 2. Excessive OfferThe offered good must be so large or in excess that it is irresistible in the context. 3. Poor JudgmentThe offer leads individuals to exercise poor judgment in an important decision. 4. Risk of Serious HarmThe individuals poor judgment leads to sufficiently high probability that he or she will experience a harm that seriously contravenes his or her interests (2005). The problem with this set of criteria is it presupposes that undue inducement is contingent upon only the consequences that result from an individuals decision, meaning that undue inducement occurs only when a poorly
References
Ashcroft, R. E. 2011. Personal financial incentives in health promotion: where do they fit in an ethic of autonomy? Health Expectations 14(2). Azetsop, J. and Rennie, S. 2010. Principlism, medical individualism, and health promotion in resource-poor countries: can autonomybased bioethics promote social justice and population health? Philosophy, Ethics, and Humanities in Medicine 5(1). Ballantyne, A. 2008. Benefits to Research Subjects in International Trials: Do They Reduce Exploitation or Increase Undue Inducement? Developing World Bioethics 8(3): 178-191. Beauchamp, T. L. and Walters, L. 2003. Contemporary Issues in Bioethics. Belmont: Wadsworth Publishing. Emanuel, E. J. 2005. Undue Inducement: Nonsense on Stilts? The American Journal of Bioethics 5(5). Johnson, R. 2012. Kants Moral Philosophy. The Stanford Encyclopedia of Philosophy (Summer 2012 Edition). Available at: http://plato.stanford.edu/entries/kant-moral/ Klitzman, R. 2013. How IRBs view and make decisions about coercion and undue influence. Journal of Medical Ethics 39: 224229. Klitzman, R. 2005. The Importance of Social, Cultural, and Economic Contexts, and Empirical Research in Examining Undue Inducement. The American Journal of Bioethics 5(5):19-21. Protection of Human Subjects, 45. C.F.R. pt. 46. 2009. Available at: http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46. html#46.111 Protection of Human Subjects, 21. C.F.R. pt. 50. 2012. Available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFRSearch.cfm?CFRPart=50&showFR=1&subpartNo de=21:1.0.1.1.19.2 US Department of Health, Education, and Welfare. 1979. Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Available at: http://www.hhs.gov/ ohrp/humansubjects/guidance/belmont.html US Department of Health and Human Services. 1993. Institutional Review Board Guidebook. Available at: http://www.hhs.gov/ ohrp/archive/irb/irb_guidebook.htm US Food and Drug Administration. 2010. Payment to Research Subjects- Information Sheet. Guidance for Institutional Review Boards and Clinical Investigators. Available at: http://www.fda. gov/RegulatoryInformation/Guidances/ucm126429.htm
Conclusion
Article
Sarah Mayes
A rapidly expanding understanding of genomics has introduced the possibility of genetically enhancing humans. Nonessential genetic enhancements may be realized in three ways: screening out the bad, selecting for the good, and engineering novel traits. With respect to parental attitudes, common deontological objections to genetic enhancementthat enhancement is wrongly motivatedsuggest it encourages parental hubris, restricts childrens freedoms, and commodifies children. These deontological objections fail to consider parents humaneness. Namely, in deciding to have a child, parents already ascribe personhood and value to this child. Enhancement merely sets an expectation for a desired outcome and does not equate to loving a child only if that outcome is achieved. Therefore, parents capable of accepting their children while encouraging them to reach their full potential may permissibly enhance their children. Although other factors such as socioeconomic discrimination must be considered in a full discussion of the ethics of enhancement, this paper evaluates genetic enhancement solely in the context of the parent-child relationship and is meant to discuss one portion of the overall discussion of enhancement.
Introduction
Parents spend incredible amounts of money, time, and effort on baseball coaching, SAT tutoring, counseling, and other modes of personal development for their children. The life work of countless parents consists of providing a means for their children to reach their full potential as human beings. Although typically thought of in abstract, unquantifiable terms, this potential is thought to be partly determined by the genotype of each particular child. What has previously been left to chance is now becoming feasibly adjustable with the rise of genetic enhancement technologies. For instance, the Genetics and Public Policy Center at Johns Hopkins University announced in 2005 that genetic modification of the germline is possible in animals but not yet in humans (Baruch et al. 2005). Researchers are pursuing the possibility of inserting new genes into human germlines. This advancement may one day allow parents to control the genetic makeup of their children and may open up a Pandoras box of concerns. Such concerns include the inherent nature of altering the genetic makeup of children and the practical societal implications of only the affluent having the means to do so. According to the former Presidents Council on Bioethics during the Bush administration, the parent-child relationship is the locus of ethical concern and agency in larger issue of genetic enhancement (2003). The ethics of genetic enhancement not only concerns the procedure and result, but also parental agency in selecting for genetic enhancement. The ability to engineer qualities into a child may affect the manner in which the parent relates to the
University of Virginia, skm5yd@virginia.edu
child. To examine the ethical permissibility of genetic enhancement in terms of parental attitudes, I will first define enhancement and then establish three types of possible genetic enhancements. I then argue that common objections to genetic enhancement in regards to parental attitudes fail in a deontological frameworkwhether an action is right or wrong based on the motiveand given the resulting discussion on the parent-child relationship, I conclude that parents may permissibly enhance their children.
Defining Enhancement
Before examining the ethics of enhancement, one must necessarily distinguish enhancement from targeting disorders. Julian Savulescu, Professor of Practical Ethics at the University of Oxford, describes the essence of enhancement as something which makes our lives better the fulfillment of nonessential, but perhaps important, interests (2006). Enhancement includes procedures to introduce characteristics that beneficially exceed the norm for a given population. In contrast, treatments bringing an individual up to par with the rest of the population are not considered enhancement. The qualifier nonessential, in contrast to normal, is required to distinguish enhancement from therapy. In this context, I define nonessential enhancement as an interruption of characteristics that a person naturally possesses and does not contribute to that persons ability to function independently. A treatment, on the other hand, would describe a procedure that remedies a loss of normal human function that may prevent or reduce a persons ability to function independently.
26
The former Presidents Council on Bioethics, under the leadership of Leon Kass, described in 2003 three methods of increasing genetic control for parents: (1) eliminating the bad (screening out), (2) selecting the good (choosing in), and (3) redesigning for the better (fixing up) (2003). Nonessential enhancement concerns only selecting the good and redesigning for the better; these can be further divided based on different biological strategies for enhancement. With respect to selecting the good, two categories will be considered: (1) selecting for traits that
As stated previously, parental attitudes offer one important set of ethical concerns that could arise with enhancement. With enhancement defined and the future possibilities outlined, we come to examining the ethical permissibility of enhancement. Specifically, we deontologically examine enhancement in terms of parental attitudes and the common objections that opponents of genetic enhancement put forth.
Beyond parental hubris, the Presidents Council on Bioethics worries about expanding parental choice and mastery over the next generation (2003). They are concerned that each generation will tyrannically impose its ideals on the next, controlling the destiny of children in a manner that is deontologically impermissible and violating of their autonomy. Although parents may one day select for traits that would not have been expressed without intervention, the child still does not experience any loss of freedom due to enhancement despite such a claim seeming initially counterintuitive. John Davis argues that arranging a genetic endowment is not problematic because by doing so, parents are essentially creating a different child after choosing to enhance (2008). The freedom of a non-endowed/non-enhanced child to remain as such is not usurped because that child simply does not exist in the first place. Similarly, there is no destiny or autonomy to violate for a child that does not exist, and neither is the autonomy of a theoretically enhanced child violated any more than that of a child nowadays. A child already does not choose his parents, so he has no say in which genetic characteristics and what quality of parental upbringing is available to him.
Finally, with the prospect of selecting traits for children comes a common deontological fear of commodification. A science-fiction scene depicts parents selecting traits from a long list to create their vision of a perfect child, making children now commodities based on the value of the selected traits. Although keeping in mind the technological infeasibility of this situation, a strong initial reaction to this picture causes many to shudder. While this fear is frightening and legitimate, it fails to give credit to parents humanness for the same reasons that parental love can be unconditional. Similar to the ideas of Kahane, Savulescu, and Wilkinson, although people may initially be attracted to certain characteristics in others, the development of love finds its roots in the person himself and not in the value of those traits (Nozick 1977). The desire to be valued and attribute value to others is not based on ones intellect, athletic ability, or physiquebut rather in ones character. Allen Buchannan, Professor of Philosophy at Duke University, concurs that selecting genetic enhancements for children would not open the door for parents to regard their offspring as manufactured items because human
Conclusion
This paper offers an in-depth analysis of the ethical considerations that parental attitudes raise for genetic enhancements. I do not claim to offer a comprehensive answer to the question of whether genetic enhancements are ethically permissible. For example, concerns regarding socioeconomic inequalities, gender differences, and the possibility of genetic influences on human nature itself are necessary for a full exploration of the acceptability of genetic enhancements. However, it remains that genetic enhancement is deontologically acceptable in terms of parental attitudes. Parental choice to enhance is not rooted in hubris and instead can be altruistic in nature. Genetic enhancement does not limit childrens freedoms, nor does it imply conditional love or commodification of children. Although exceptions always exist in which parents may not demonstrate expected levels of humanness, this paper demonstrates that genetic enhancement fails to violate deontological concerns in the case of the parent capable of love.
References
Baruch, S. et al. 2005 Human Germline Genetic Modification: Issues and Options for Policymakers Genetics and Public Policy Center. Washington, DC. Bess, M. 2010. Enhanced Humans vs. Normal People: Elusive Definitions. Journal of Medicine and Philosophy 35(6): 641-655. Buchanan, A. 2008. Human Nature and Enhancement. Bioethics, Malden, MA: Blackwell. Davis, J. 2008. Selecting Potential Children and Unconditional Parental Love. Bioethics, 22: 258. Kahane, G. & Savulescu, J. 2009. The Moral Obligation to Create Children With the Best Chance of the Best Life. Bioethics 23(5): 274-290. Kamm, F. 2005. Is There a Problem with Enhancement?. The American Journal of Bioethics, 5: 3-14. Nozick, R. 1977. Anarchy, State and Utopia. New York, NY: Basic Books. Presidents Council on Bioethics. 2003. Beyond Therapy General Reflections. Beyond Therapy, chapter 6. Presidents Council on Bioethics. 2002. Council discussion of The Birth-Mark, Nathaniel Hawthorne, led by William F. May, Ph.D. Sandel, M. 2004. The Case against Perfection. Atlantic Magazine. Savulescu, J. 2006. Justice, Fairness, and Enhancement. Annals of the New York Academy of Science 1093: 5. Schwartz, P. 2005. Defending the Distinction Between Treatment and Enhancement. American Journal of Bioethics 5(3): 17-19. Wilkinson, S. 2010. Choosing Tomorrows Children: The Ethics of Selective Reproduction. Oxford.
29
30
31
bioethicsjournal.com
32