Princeton Journal of Bioethics - 2009 by Princeton Journal of Bioethics

Volume X Spring 2009

PJB Princeton Journal of Bioethics

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

Vol. X Spring 2009

The Princeton Journal of Bioethics Rachel Rizal ‘09 Vinay Shah ‘09 Editors-in-Chief Tony Trenga ‘11 Layout Editor Paul Ginart ‘10 Anupama Pattabiraman ‘10 Andrew Yang ‘09 Editorial Staff

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Foreword

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

Martin Eichelberger, MD Chief of Trauma and Burn Services, Children’s National Medical Center; Director of Safe Kids Worldwide Eric Gregory, PhD Assistant Professor of Religion, Princeton University Irene Jillson, PhD Assistant Professor in the School of Nursing and Health Studies, Georgetown University Daniel Notterman, MD Professor of Molecular Biology, Princeton University Peter Singer, B.Phil Professor of Bioethics in the University Center for Human Values, Princeton University

On behalf of the staff of the Princeton Journal of Bioethics, we are pleased to present you with the Spring 2009 issue of the Journal. The articles we have selected for this issue discuss topics such as attitudes toward alpha-fetaprotein (AFP) screening in the United States and Europe, the system of egg donation in the United States, and genetic testing for susceptibility to breast cancer. We hope that you find this issue stimulating. The articles included in the Journal are first submitted by undergraduate students from around the country to the Princeton Journal of Bioethics Editorial Board. The Board then compiles, edits, and publishes this work. As our fine tradition of publishing the best undergraduate work in bioethics depends on student submissions, we encourage you to send us papers relevant to bioethical topics so that we may consider them for upcoming issues of the Journal. We could not have published the Journal without the guidance of our Technical Review Board. These prominent experts ensure the accuracy and quality of our publication. We would also like to thank Princeton’s departments of Molecular Biology and Philosophy. Their generous support helped make this year’s publication possible. Thank you for your continued support and interest in the Princeton Journal of Bioethics. We hope that the Journal provides you with new perspectives and material to ponder, debate, and discuss. It is only through sustained dialogue and awareness that progress in bioethics can be made, and we invite you to become an active participant in this exciting and rapidly growing field. Sincerely, Rachel Rizal ‘09 Vinay Shah ‘09 Editors-in-Chief

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Vol. X Spring 2009

The Princeton Journal of Bioethics Volume X, 2009 Contents

Foreword Rachel Rizal ‘09 and Vinay Shah ‘09 Princeton University

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Testing for BRCA1/2 Mutations: A Personal, Social, and Economic Issue Alexandra Berger ‘10 University of Pennsylvania

Alpha-fetoprotein Screening for Fetuses with Neural Tube Defects: A Comparative Analysis of its Rise in Europe and America Danny Mammo ‘11 Duke University

The Ethics of Egg Donation Jacquelyn Hatch Brown University

Bioethics and Public Diplomacy: Dialogue through Shared Concerns, Vital Questions Irene Anne Jillson, PhD

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The Princeton Journal of Bioethics

Vol. X Spring 2009

Testing for BRCA1/2 Mutations: A Personal, Social, and Economic Issue Alexandra Berger University of Pennsylvania

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

Testing for mutations in BRCA1/2 that code for a susceptibility to breast cancer involves an extremely complicated decision making-process. Since its discovery in 1994, BRCA mutation has been widely studied as the cause of early onset breast cancer. Although women that inherit this mutation will not necessarily develop the disease, they have an extremely high likelihood of doing so. For this reason, at risk women could drastically benefit from genetic testing for this disease. However, the decision to test is extremely complicated one. Women must weigh their quality of life following testing against their increased post-testing lifespan. The choice is made more complicated by the social and economic issues that govern testing. Socially, women must weigh factors of informed consent, the right not to test, prenatal testing, and privacy. Privacy is closely related to economic factors, especially to insurance discrimination. In nations with privatized health care systems, women are potentially faced with raised insurance rates due to positive test results. To respond to this type of discrimination, the United States Congress passed the Genetic Information Nondiscrimination Act of 2005. Testing in countries with nationalized healthcare systems, such as in the United Kingdom and Canada, is widely provided free through these systems, which removes the fears of insurance discrimination. Thus, testing for breast cancer susceptibility through BRCA screening is an extremely complicated issue that encompasses personal, social, and economic considerations and serves as symbol of contemporary fears of the increased geneticization of modern society. It is important note that all cancer has a genetic component, but there is a distinct difference between the genetic nature of cancer and a hereditary susceptibility for the disease1. Although most breast cancer is caused by the “genetic alterations of somatic cells of the breast,” most breast cancer is not hereditary1. The hereditary nature of breast cancer was first examined by Mary-Claire King and her team in 1990 and was outlined in their paper “Linkage of Early-Onset Familial Breast Cancer to Chromosome 17q21.” In their study, King, using the linkage analysis of “23 extended 1 Hall, Jeff, Lee, Ming, Newman, Beth, Morrow, Jan, Anderson, Lee, Huey, Bing, and King, Mary-Claire. “Linkage of Early-Onset Familial Breast Cancer to Chromosome 17q21.” Science 250.4988 (1990): 1684-1689. (1684).

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families with 146 cases of breast cancer,” determined that in all likelihood the susceptibility gene did exist and that it was located on chromosome 171. The actual gene was not discovered until 1994 and was revealed by a different team. The gene was found to exist on the longer arm of the chromosome previously discussed by King2. It was officially named BRCA1, which stood for breast cancer 1, early onset3. Today, we have an increased understanding of the function of BRCA1, as well as its counterpart BRCA2, which was discovered in 19954 (Wooster). These two genes are part of a group which, in normal expression, act to suppress the growth of tumors by regulating the reproduction of somatic cells. BRCA1 and 2 in particular prevent tumorogenesis in the milk ducts of the breast. When mutations exist in these two genes, this can inhibit the part of expression that codes for the normal function of repairing damaged DNA in the cells. This can cause cells to reproduce uncontrollably, which can lead to tumor production3. Victims of inherited susceptibility account for only 5% to 10% of all breast cancer cases, but if one inherits a mutation, they have a “50% to 85% chance of developing breast cancer by age 70 years and a 16% to 60% risk of developing ovarian cancer”5. Additionally, carriers have a 50% chance of giving birth to a child with a susceptibility, as the trait follows the traditional Mendelian pattern of a dominant allele6. Because of the high risk of breast cancer among those who inherit a mutation in these two genes, many women with a high incidence of the disease in their family would benefit from a genetic test for susceptibility. However, “laboratory testing for all possible mutations is challenging”7. Because there are over 600 possible mutations, it is extremely difficult at this point to screen for an abnormality in a woman with limited history of breast cancer in her family3, 7. It is essential in most cases that the woman 2 Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, et al. “A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.” Science 266.5182 (1994): 66-71.(66). 3 “BRCA1-Genetics Home Reference.” May 2006. U.S. National Library of Medicine. 29 November 2006 <http://ghr.nlm.nih.gov/gene=brca1;jsessionid=F6BA5381DE65E85C4C29 9603544102AD>. 4 Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, Nguyen K, Seal S, Tran T, Averill D, et al. “Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13.” Science 265.5181 (1995): 2088-2090. 5 Holland-Frei. “Genetic Basis of Cancer Syndromes: Breast-Ovarian Cancer Syndrome.” Cancer Medicine 6. London: BC Decker Inc, 2003. 6 Szabo CI, King MC. “Inherited Breast and Ovarian Cancer.” Human Molecular Genetics 4 (1995): 1811-1817. (1811). 7 Coughlin, Stephan, Khoury M, Steinberg K. “BRCA1 and BRCA2 gene mutations and risk of breast cancer: Public health perspectives.” American Journal of Preventative Medicine 16.2 (1999): 91-98. (91).

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have multiple family members that have already been affected, so that the physician knows exactly the mutation for which he is searching8. This reduces the risk of a false-negative test result. To determine if there is an abnormality, direct DNA sequencing or single-strand conformation polymorphism assay can be used, and once a mutation is determined in a family, the faster allelespecific oligonucleotide hybridization works as well7. Woman who test positive for a susceptibility have a few choices. The first is general surveillance. This includes regular physical examination by a professional (at least twice a year), and in patients older than 30, regular mammography. The second option, that of prophylactic mastectomy, is far less desirable. This surgery, which removes most of the breast tissue has been shown to dramatically reduce the risk of breast cancer. However, it should be noted that a risk still remains, as it is impossible to remove all the affected tissue9. Also an option is prophylactic oophorectomy, or the removal of the ovaries. This completely eliminates the risk of ovarian cancer and may reduce breast cancer risk as well8. Currently, the use of prophylactic Tamoxifen, a drug traditional to chemotherapy, is being explored too. The choice whether or not to get tested for breast cancer susceptibility is extremely complex, encompassing not only the emotional issues stemming from possible mastectomy, but also social, economic, and political issues as well. It is important to study the decision-making process involved with deciding to test, examining the factors that contribute to the determination. One primary source that addresses this issue is “Assessing the Benefits of Testing for Breast Cancer Susceptibility: A Decision Analysis.” Written in 1998, the researchers use a scientific model for predicting the best decision for women debating whether or not to get tested. The method they propose is based on the calculation of a QALY, or quality-adjusted life year compared with years of survival. A QALY is a year that “is discounted to take into consideration any negative aspects of health states (cancer, prophylactic interventions, etc.) present in that year”10. These values are to be based on the predictions of women assessing their future quality of life. Berry proposes that women should attempt to determine how valuable a year negatively affected by health issues would be in comparison to a normal year. “For example, a year subsequent to bilateral mastectomies may equal 8 Szabo CI, King MC. “Inherited Breast and Ovarian Cancer.” Human Molecular Genetics 4 (1995): 1811-1817. (1812). 9 Berry, Donald, Giovanni, Parmigiani. “Assessing the Benefits of Testing for Breast Cancer Susceptibility Genes: A Decision Analysis.” Breast Disease 10.1 (1998): 115-125. (116). 10 Berry, Donald, Giovanni, Parmigiani. “Assessing the Benefits of Testing for Breast Cancer Susceptibility Genes: A Decision Analysis.” Breast Disease 10.1 (1998): 115-125. (117).

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0.9 QALY for a woman who rates such a year as 10% less valuable than a year of life in perfect health”9. This value is especially important in the case that a woman would opt for prophylactic mastectomy upon learning that she is positive for BRCA mutation. According to the author, “Testing is beneficial for the woman in this example because her optimal decision is mastectomies in one case (positive result) and no mastectomies in the other (negative) result. Testing is not beneficial for a woman who would chose the same intervention in both cases (e.g. one who would avoid mastectomy if the test is positive and also if it is negative)”11. Thus, according to the paper, women should only opt for testing if they are willing consider prophylactic mastectomies as methods of treatment in the case that they are found to be positive for the mutation. Women who will not consider this option should not make the decision to test because if they are not willing to take the preventive measures, they will just experience cancer worry which will inhibit their quality of life. This said, Berry does agree that a woman who is not willing to pursue prophylactics might still wish to test because she might want to “inform members of her family about their risk...or she ‘may just want to know’”10. This issue of informing other family members is extremely important to many in deciding to test. One woman, after finding out that she had the susceptibility gene commented (in reference to the decision to provide a sample to the study) “...I do this for everyone in the family”12. Much of the decision to test, Berry argues, must also come down to the likelihood, based on the family history, that the subject will test positive for a mutation. Using a family history, it is possible to calculate the chance of a positive diagnosis: “...clinicians and counselors can integrate and interpret pedigrees, historical data, physical findings, and laboratory data, providing individualized probabilities of various outcomes”10. Obviously, the more likely the patient is to have the mutation, the more likely it is that she should test. The majority of the scientific data in this paper focuses on balancing survival, quality of life, and likelihood of disease as central elements in making the decision to test for BRCA1/2 mutations. However, the author does mention that these more practical elements must interact with extenuating circumstances in the decision-making process. These factors are far more difficult to quantify and as such, no attempt to do so is made in the paper. That said, social, political, and economic implications are essential in 11 Berry, Donald. (118) 12 Goelen, G, Rigo A, Bonduelle, M, and De Greve, J. “Moral Concerns of Different Types of Patients in Clinical BRCA1/2 Gene Mutation Testing.” Journal of Clinical Oncology 17.5 (1999): 1595-1600. (1599).

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the question of testing and must be carefully examined before the decision is made. According to Berry, “[f ]or some women, testing can lead to improved health conditions. However, such improvements must be weighed against issues such as cost, privacy, and the possible loss of insurance”13. In today’s rapidly expanding technological world, fears of geneticization are mounting and as such the issue of genetic testing always faces issues of confidentiality, patient rights, and other social considerations. These issues are outlined in “Ethical implications of genetic testing for breast cancer susceptibility.” According to Surbone, the author, there are essential ethical implications to the issue of BRCA testing. Surbone first discusses the issue of “Information and informed consent”14. According to her, “...informed consent is the absolute prerequisite for any genetic testing.”13 This, therefore, is an essential social issue with BRCA testing. Mass media must spread information on breast cancer screening in order for applicable individuals to learn how they might be helped by the process. As of now, the majority of those that get tested are of the highly educated elite, because of the nature of the spread of new technologies from those who have higher education to those who are less exposed15. “Low-income, minority, and uninsured women may find specific socioeconomic barriers to obtaining health-related data and education”16. Those who are not properly informed about the nature of the test for BRCA cannot make an accurate decision as to whether or not testing is beneficial to them. This also relates to the necessity of creating a system of counseling to advise both those who are deciding to begin the process and those who are dealing with the results of the testing. Counseling is important preemptively to ensure that the patients make decisions that are in their best interest based on the factors Berry mentioned, namely the likelihood of a positive test result and quality of life issues. Counseling is essential after the subject receives the results of their test as well because the “provision of genetic information without proper counseling and follow-up could lead to psychological distress and impair adherence to recommendations for the early prevention of breast 13 Berry, Donald. (124). 14 Surbone, A. “Ethical implications of genetic testing for breast cancer susceptibility.” Critical Reviews in Oncology/Hematology 40.2 (2001): 149-157.(151). 15 Steel, M, Smyth, E, Vasen, H, Eccles, D, Evans, G, Møller, P,, Hodgson, S, StoppaLyonnet, et al. “Ethical, Social and Economic Issues in Familial Breast Cancer: a compilation of views from the E.C. Biomed II Demonstration Project.” Disease Markers 15 (1999): 125131.(126). 16 Peterson, E, Milliron, K, Lewis, K, Goold, S., Merajver, S. “Health Insurance and Discrimination Concerns and BRCA1/2 Testing in a Clinic Population.” Cancer Epidemiology Biomarkers and Prevention 11.1 (2002): 79-87. (79).

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cancer”17. The second ethical issue discussed is that of the right to be tested or not. Surbone explains that “in most cultures of nondirective genetic counseling...the choice of whether or not to pursue genetic testing is left to the individual. Such a standpoint implies the more or less explicit acknowledgment of a ‘right not to know’”18. This is an extremely complicated issue because some argue that complete autonomy requires testing as the individual cannot make an informed decision about their treatment unless they are tested. “In no way is therefore the ‘right not to know’ a given in the present ethical debate”17. The debate is made more complicated by the fact that the outcome of a test also affects the family of the individual patient. Surbone questions, “Does the daughter of a cancer patient have the right to know her mother’s BRCA status?” On the lines of informing affected family, it is also important to consider the affect that a positive result will have on the reproductive decisions made by the tested individuals. Ethically, is it the duty of a woman with a high incidence of bilateral breast cancer in her family to test before she decides to have children? This has an affect on the decisions of many women to get tested19. The issue goes beyond testing potential mothers for the trait, although. The prospect of prenatal testing for BRCA mutations is already a reality. “The central argument in favour of the prenatal molecular genetic diagnosis of BRCA1 mutations stems from the suffering and exceptional psycho–social burden experienced by parents with a family background marked by a high incidence of breast and ovarian cancers and the deaths that result from these diseases”20. Thus, those women who test positive for the susceptibility may want to remove that same burden from their children and opt for prenatal testing to insure that their fetus is not one of the 50% of their offspring that will inherit the same condition. This creates a myriad of other issues, such as that of elective abortion to prevent the birth of affected children and the decision to inform a child that is born with mutation of their condition. Possibly the most important consideration many face when deciding whether or not to go forward with testing for breast cancer susceptibility is the issue of privacy. Privacy and confidentiality are extremely relevant to 17 Coughlin, Stephan. (94). 18 Surbone, A. (151). 19 Goelen, G. (1599). 20 Wagner, T, Ahner, R. “Debate: Prenatal testing for late-onset diseases such as mutations in the breast cancer gene 1 (BRCA1) Just a choice or a step in the wrong direction?” Human Reproduction 13.5 (1998): 1125-1128. (1126).

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breast cancer screening and involve social, political, and economic issues. “In the field of genetics there is the special issue of whether information about heritable factors can be regarded as the ‘property’ of any one individual rather than belonging to all who share the same inheritance”21. If a woman tests positive for a BRCA mutation, should that information be confidential? Socially, should this woman feel obligated to inform her husband? Her friends? If a woman reveals her positive status to a potential life partner, this could affect his willingness to engage in a marriage, knowing full well that her life will most-likely be cut short and that any offspring they have might be similarly affected. The issue of privacy is essential to a discussion of the problem of discrimination in insurance and the differences between experiences of victims living in countries that rely primarily on private insurance versus those that have a socialized health care system. However, before one evaluates the affect of insurance on the decision to test for susceptibility, it is essential to examine the general economic factors that inform this decision. Currently, the majority of women seeking testing for BRCA mutation belong to the wealthy upper class. Although this could be explained by the dissemination of knowledge from the top down, it could also be due to the increased ability of the individuals to pay for the testing. Full sequencing of BRCA1/2 costs $2,400 dollars, and most are unable to afford this price22. Thus, in countries without socialized health care, most are forced to rely on their insurance to pay for the test, if they are willing to get tested at all. Another economic issue is that of the commercialization of the testing method. “The ability of health care providers to constrain access to BRCA testing has been threatened by the patenting and commercialisation of the BRCA genes by the American diagnostics company Myriad Genetics with its broad U.S. and Canadian patent...”23. The commercialization of BRCA has caused a hike in the price of testing and has raised ethical issues. The company advertises expansively to “both physicians and the general public” and their marketing has “been criticized for being reductionist, deterministic, and for exploiting public anxiety about breast cancer as a way to convince people that they need and should purchase (or demand from their physicians) an expensive genetic test that is unlikely to be clinically 21 Steel, M. (127). 22 Berry, D. (115). 23 Williams-Jones, B, Burgess, M. “Democritising access to genetic services.” Familial Cancer 5 (2006): 117-121. (119).

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useful”24. The Myriad test has inherent flaws because, as I mentioned before, it is only effective among women with an extensive history of breast cancer in their families. For this reason, it is extremely misleading for the company to market their product to the average consumer because these individuals would most likely not benefit from the test. Their extensive advertising campaign also raises the price of testing for those who would benefit from the test, which is ethically debatable. Myriad’s monopoly on BRCA testing and the subsequent rise in the cost of the test has a large affect on the involvement of insurance in the testing process. According to the Myriad website, “Testing for hereditary cancer risk is becoming more common, especially as healthcare provides new options for cancer risk reduction to physicians and patients. Most insurance carriers cover genetic testing services. In fact, although each situation is unique, the average patient pays only 10% of the test price out-of-pocket”25. That said, the insurance situation in the United States and other countries is not as simple as the company would like its potential clients to think. In the United States, where health insurance is privatized, many women must consider their insurance before making the decision to test for breast cancer and this creates a unique set of problems before, during, and after testing. “[F]ear of discrimination is one of the most common reasons given for declining BRCA1/2 testing in clinical population, even overshadowing fear of a positive result”26. The dramatic effect of potential detriment to ones health insurance is explained by Emily Peterson in her study, “Health Insurance and Discrimination Concerns and BRCA1/2 testing in Clinical Population.” In this paper, she explores the degree to which insurance concerns impede the desire of endangered woman to follow through with testing. Peterson took a cohort of women who had originally been seen in one of two clinics based on their risk of breast cancer and “compared those who ‘pursued testing’ to those who ‘declined testing’ and those who ‘pursued testing’ to a subgroup of patients who ‘declined because of insurance/discrimination concerns’”27. The results were striking. 42% of the individuals in the study declined genetic testing. Of these, 62% declined due to their fears of insurance discrimination, cost, and/or confidentiality. That means that in this study, 26% of individuals, half of whom had already

been diagnosed with cancer or a related disease, refused testing in large part because they were afraid it would affect their insurance coverage. Interestingly, the largest group of women did assume that their insurers would pay for the genetic test if they had decided to disclose it. Of those who did decide to go through with the testing, 15% “had chosen to pay for all of their services privately, intentionally not involving insurance providers.” All of these patients explained that they had done so because of fears of discrimination for themselves or their children. The rest of the patients that received testing “reported efforts they made to attempt to procure payment for testing services”28. This included calls made to representatives, writing letters to request coverage, gathering letters of medical necessity, and other time-consuming measures. Despite these difficulties, which exceed normal the processes for obtaining coverage, all of the woman who attempted to go through insurance were covered. The issue of result disclosure was also an essential element to the decision making process. The majority of individuals admitted that having their results kept confidential from their insurers affected their testing decision, although most claimed to have no problem revealing their results to their families29. The issue of insurance affecting a woman’s likelihood of getting tested is extremely dangerous for the woman affected. It was estimated that 14% of woman in the Peterson study did not learn of their positive test result due to fears of insurance discrimination28. This relates both to the decision to rely on insurance coverage for payment for the test and whether or not to disclose the results of testing to the insurer. It is important, however, to examine the issue from both sides of the debate. “[H]ealth insurers may face large outlays if initial testing results in extensive testing of family members”30. For this reason, it may be increasingly difficult for many companies to pays for the provision of these tests. The Myriad commercialization of the test has made the issue even more difficult as this has caused an increase in the price. Companies in the future will also be forced to weigh the benefit of early testing against the high cost of insuring a cancer patient. For example, if a woman in her twenties gets a positive test result and opts for prophylactic mastectomies, would it be in the best interest of the insurance company to cover this surgery with the promise of saving money if because of it the woman does not succumb to cancer later? There is also the idea of actuarial

24 Williams-Jones, B. (120). 25 “Myriad Reimbursement Assistance Program (MRAP).” 29 November 2006. <http:// www.myriadtests.com/mrap.htm>. 26 Peterson, E. (79). 27 Peterson, E. (82).

28 Peterson, E. (83). 29 Peterson, E. (85). 30 Philips, K, Veenstra, D, Ramsey, S, Van Bebber, S, Sakowski, J. “Genetic Testing and Pharmacogenomics: Issues for Determining the Impact to Healthcare Delivery and Costs.” The American Journal of Managed Care 11.7.1 (2004): 425-432. (429).

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fairness. “Based on the rationale that genetic predisposition constitutes a preexisting condition, health insurance can be denied with the alleged justification that adverse selection could occur.”31 Actuarial fairness is a far cry from moral fairness and rationalizes dropping potential cancer patients because the companies cannot profit in the laissez fare economy if they cover them31. The effect of testing on life insurance coverage has also been evaluated. One study completed at the University of Pennsylvania School of Medicine evaluates this aspect of testing. The team analyzed a cohort of woman that were participating in the “Breast Cancer Evaluation Program,” which was created to “provide breast cancer risk assessment, genetic counseling, and genetic testing for breast caner susceptibility to interested individuals”32. After evaluating the group of women, the researchers found that the majority of women rated life insurance discrimination as a moderately or very important factor in deciding to go through with testing. No woman, however, reported that her life insurance provider had dropped or changed her coverage based on the test results. It is interesting that “although concern about insurance discrimination is high, [they] found no evidence of actual life insurance discrimination among women who participated”33. A small percentage (4%) of the women decided to increase their life insurance policy following testing, a sign that a positive test result is linked to a desire in women to raise their coverage32. Fears of both health and life insurance discrimination in the United States have culminated in the passage of two laws that address this issue in an attempt to provide protection to affected women. The first of these is the Health Insurance Portability and Accountability Act (HIPAA), passed in 1996 by Congress. The law states, that “a group health plan, and a health insurance issuer offering group health insurance coverage in connection with a group health plan, may not establish rules for eligibility...of any individual to enroll under the terms of the plan based on...[g]enetic information”34. In essence, after the law was passed, it became illegal for group health insurers to discriminate against their clients based on any information about existing 31 Surbone, A. (153). 32 Armstrong, K, Weber, B, FitzGerald, G, Hershey, J, Pauly, M, Lemaire, J, Subramanian, K, Asch, D. “Life Insurance and Breast Cancer Risk Assessment: Adverse Selection, Genetic Testing Decisions, and Discrimination.” American Journal of Medical Genetics 120A (2003): 359-364. (360). 33 Armstrong, K. (362). 34 United States. Cong. Senate. 104th Congress. Public Law 104-191 Health Insurance Portability and Accountability Act [introduced in the U.S. Senate; 21 August, 1996] HIPAA. ORG. 29 November, 2006 <http://aspe.hhs.gov/admnsimp/pl104191.htm> . (Title 1).

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genetic conditions. However, there were many difficulties with enforcement of the act. According to a study completed in 1998, the HIPAA did not prohibit “raising the rates of the entire group” covered by the insurer based on genetic information about that individual, but only prevented a hike in the insurance rate on a single individual covered in a group context35. Also, the legislators neglected to define the meaning of “genetic information,” a loophole that might have had dangerous consequences34. As a follow up to the HIPAA, Congress passed the Genetic Information Nondiscrimination Act of 2005, which was far more detailed than its predecessor. Congress made the following finding: Deciphering the sequence of the human genome and other advances in genetics open major new opportunities for medical progress. New knowledge about the genetic basis of illness will allow for earlier detection of illnesses, often before symptoms have begun. Genetic testing can allow individuals to take steps to reduce the likelihood that they will contract a particular disorder. New knowledge about genetics may allow for the development of better therapies that are more effective against disease or have fewer side effects than current treatments. These advances give rise to the potential misuse of genetic information to discriminate in health insurance and employment.36 The act carefully addresses these considerations. The bill initially proposes that “a group health plan...shall not adjust premium or contribution amounts for a group on the basis of genetic information concerning an individual in the group or a family member of the individual...”37. Thus, this act clearly prevents discrimination in insurance rates based on the results of a genetic test. Second, it states that a “group health plan, or a health insurance issuer offering health insurance coverage in connection with a group health plan, shall not request or require an individual or a family member of such individual to undergo a genetic test”36. Essentially, a health insurer is prevented from forcing an individual from completing a genetic test against his or her will. Significantly, the act also defines the term “genetic 35 Dressler, Lynn. “Genetic Testing for the BRCA1 Gene and the Need for Protection from Discrimination: An Evolving Legislative and Social Issue.” Breast Disease 10.1.2 (1998): 127-135. (130). 36 United States. Cong. Senate. 109th Congress. S.306 Genetic Information NonDiscrimination of 2005 [introduced in the U.S. Senate; 16 February 2005]. GovTrack.us. 29 November, 2006 <http://www.govtrack.us/congress/bill.xpd?bill=s109-306>. (Section 2). 37 Genetic Information Non-Discrimination Act of 2005. (Section 101).

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information,” describing it as “information about (i) an individual’s genetic tests; (ii) the genetic tests of family members of the individual; or (iii) the occurrence of a disease or disorder in family members of the individual”36. The Genetic Information Nondiscrimination Act addresses the concerns expressed by many that their insurance coverage would change if they revealed the status of their BRCA mutation test. In countries with socialized healthcare systems, the issue of payment for genetic testing is slightly different. Great Britain has a National Health Service (NHS), which exists simultaneously with private insurance. Studies have addressed issues of private insurance discrimination fears in this context as well, with similar results to American studies38. However, most of the genetic testing, including that for BRCA mutation is completed through the NHS. When the BRCA genes were discovered in the mid-1990s, regional genetics clinics run by the UK National Health Service (NHS) also began to develop services to test for BRCA mutations. The clinics modeled their systems on other genetic testing services they provided – as a package of counseling and laboratory analysis connected to specialist and primary care physicians through a hierarchical referral network...BRCA testing in the UK was governmentsponsored and oriented towards preventive care.39 Originally the majority of BRCA1/2 testing was organized in harmony with the NHS, with clinics either opting to provide free testing to all who wanted it, or choosing to cover testing only to those clients with extensive family history of the disease40. This method of testing has been far more successful in assuaging clientèle fears over insurance discrimination. According to Parthasarathy, “[i]n a nation with a public health care system, there was less concern with preventing insurance companies from getting hold of genetic test results”41. In 1996, the NHS officially nationalized BRCA testing with the hope of providing equal access to all of the country’s citizens. Canada also has a nationalized health care system which is organized

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into Provincial Health Insurance (PHI) groups, each province controlling its citizens access42. The system is set up by the Canada Health Act (CHA), which ensures that Canadian citizens receive universal health insurance that is accessible to all43. The Canadian healthcare system has addressed the issue of BRCA testing as well. Before 2000, “[i]n most provinces in Canada, BRCA testing is provided through public health care institutions...[that] have guidelines restricting access to patients with risk factors, such as a strong family history...early age of onset...or membership in a specific ethnic group... Testing is not available to “patients off the street” with little or no family history of disease44. This method of providing free testing was extremely successful until the Canadian government granted patents to Myriad Genetics in 2000 and 2001. Because of these patents, the nationalized health system was forced to purchase only the very expensive Myriad testing systems. “[T]he government did not provide the financial resources to allow the local provider of BRCA testing, the Hereditary Cancer Program (HCP), to manage the increased cost of purchasing Myriad’s test, and thus test provision had to be halted”45. By 2003, the B.C. Minister of Health Services authorized the re-initiation non-commercialized BRCA testing. According to the Minister: “B.C. women and other future patients have a right to all the information they need to stay healthy. It is completely unethical to use patents based on genetic sequencing to block patients’ access to their own genetic information, particularly when we already have the knowledge, ability and equipment to provide women with this information.46” Testing for BRCA mutation and breast cancer susceptibility is an issue that involves the complex relationship between a variety of different factors, including personal, social, and economic considerations. Women must weigh these different aspects of decision-making before they can go through with the testing process. In our contemporary, rapidly geneticizing world, the implications of testing for BRCA mutation can be applied to a wide variety of different genetic tests and as such it is essential that we examine these concerns.

38 Watson, M, Foster, C, Eccles, D, Ashley, S, Davidson, R, Mackay, J, Morrison, PJ, Hopwood, P, and Evans, DGR. “Psychosocial impact of breast/ovarian (BRCA1/2) cancerpredictive genetic testing in a UK multi-centre clinical cohort.” British Journal of Cancer 91 (2004): 1787-1794. (1788). 39 Parthasarathy, S. “Architectures of Genetic Medicine: Comparing Genetic Testing for Breast Cancer in the USA and the UK.” Social studies of science 35.1 (2005): 5-40. (24). 40 Parthasarathy, S. (25). 41 Parthasarathy, S. (26).

42 “Provincial Health Insurance.” 29 November 2006 <http://www.canadian-healthcare. org>. 43 Canada. Parliament. House of Commons. Debates, 33rd April 1, 1984. “Canada Health Act” 29 November 2006 <http://laws.justice.gc.ca/en/C-6/text.html>. 44 Williams-Jones B, Burgess, MM. “Social contract theory and just decision making: lessons from genetic testing for the BRCA mutations.” Kennedy Institute of Ethics Journal 14.2 (2004): 115-142. (121). 45 Williams-Jones, B. “Democritising access to genetic services.” (119) 46 Williams-Jones, B. “Social contract theory and just decision making: lessons from genetic testing for the BRCA mutations.” (123).

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Works Cited Armstrong, K, Weber, B, FitzGerald, G, Hershey, J, Pauly, M, Lemaire, J, Subramanian, K, Asch, D. “Life Insurance and Breast Cancer Risk Assessment: Adverse Selection, Genetic Testing Decisions, and Discrimination.” American Journal of Medical Genetics 120A (2003): 359-364. Berry, Donald, Giovanni, Parmigiani. “Assessing the Benefits of Testing for Breast Cancer Susceptibility Genes: A Decision Analysis.” Breast Disease 10.1 (1998): 115-125.

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Holland-Frei. “Genetic Basis of Cancer Syndromes: Breast-Ovarian Cancer Syndrome.” Cancer Medicine 6. London: BC Decker, Inc, 2003. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, et al. “A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.” Science 266.5182 (1994): 66-71. “Myriad Reimbursement Assistance Program (MRAP).” 29 November 2006. <http://myriadtests.com/mrap.htm>.

“BRCA1-Genetics Home Reference.” May 2006. U.S. National Library of Medicine. 29 November 2006 <http://ghr.nlm.nih.gov/gene=brca 1;jsessionid=F6BA5381DE65E85C4C299603544102AD>.

Parthasarathy, S. “Architectures of Genetic Medicine: Comparing Genetic Testing for Breast Cancer in the USA and the UK.” Social studies of science 35.1 (2005): 5-40.

Canada. Parliament. House of Commons. Debates, 33rd April 1, 1984. “Canada Health Act” 29 November 2006 <http://laws.justice.gc.ca/en/C-6/text.html>.

Peterson, E, Milliron, K, Lewis, K, Goold, S., Merajver, S. “Health Insurance and Discrimination Concerns and BRCA1/2 Testing in a Clinic Population.” Cancer Epidemiology Biomarkers and Prevention 11.1 (2002): 79-87.

Coughlin, Stephan, Khoury M, Steinberg K. “BRCA1 and BRCA2 gene mutations and risk of breast cancer: Public health perspectives.” American Journal of Preventative Medicine 16.2 (1999): 91-98. Dressler, Lynn. “Genetic Testing for the BRCA1 Gene and the Need for Protection from Discrimination: An Evolving Legislative and Social Issue.” Breast Disease 10.1.2 (1998): 127-135. Goelen, G, Rigo A, Bonduelle, M, and De Greve, J. “Moral Concerns of Different Types of Patients in Clinical BRCA1/2 Gene Mutation Testing.” Journal of Clinical Oncology 17.5 (1999): 1595-1600. Hall, Jeff, Lee, Ming, Newman, Beth, Morrow, Jan, Anderson, Lee, Huey, Bing, and King, Mary Claire. “Linkage of Early-Onset Familial Breast Cancer to Chromosome 17q21.” Science 250.4988 (1990): 1684-1689. 14

Philips, K, Veenstra, D, Ramsey, S, Van Bebber, S, Sakowski, J. “Genetic Testing and Pharmacogenomics: Issues for Determining the Impact to Healthcare Delivery and Costs.” The American Journal of Managed Care 11.7.1 (2004): 425-432. “Provincial Health Insurance.” 29 November 2006 <http://canadian-healthcare.org>.

Steel, M, Smyth, E, Vasen, H, Eccles, D, Evans, G, Møller, P,, Hodgson, S, Stoppa-Lyonnet, et al. “Ethical, Social and Economic Issues in Familial Breast Cancer: a compilation of views from the E.C. Biomed II Demonstration Project.” Disease Markers 15 (1999): 125 131. Surbone, A. “Ethical implications of genetic testing for breast cancer susceptibility.” Critical Reviews in Oncology/Hematology 40.2 (2001): 149-157. 15

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Szabo CI, King MC. “Inherited Breast and Ovarian Cancer.” Human Molecular Genetics 4 (1995): 1811-1817. United States. Cong. Senate. 104th Congress. Public Law 104-191 Health Insurance Portability and Accountability Act [introduced in the U.S. Senate; 21 August, 1996]. HIPAA.ORG. 29 November, 2006 <http://aspe.hhs.gov/admnsimp/pl104191.htm>. United States. Cong. Senate. 109th Congress. S.306 Genetic Information Non-Discrimination of 2005 [introduced in the U.S. Senate; 16 February 2005]. GovTrack.us. 29 November, 2006 <http://www.govtrack.us/congress/bill.xpd?bill=s109-306>. Wagner, T, Ahner, R. “Debate: Prenatal testing for late-onset diseases such as mutations in the breast cancer gene 1 (BRCA1) Just a choice or a step in the wrong direction?” Human Reproduction 13.5 (1998): 1125-1128. Watson, M, Foster, C, Eccles, D, Ashley, S, Davidson, R, Mackay, J, Morrison, PJ, Hopwood, P, and Evans, DGR. “Psychosocial impact of breast/ovarian (BRCA1/2) cancer-predictive genetic testing in a UK multi-centre clinical cohort.” British Journal of Cancer 91 (2004): 1787-1794. Williams-Jones, B, Burgess, M. “Democritising access to genetic services.” Familial Cancer 5 (2006): 117-121. Williams-Jones B, Burgess, MM. “Social contract theory and just decision making: lessons from genetic testing for the BRCA mutations.” Kennedy Institute of Ethics Journal 14.2 (2004): 115-142. Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, Nguyen K, Seal S, Tran T, Averill D, et al. “Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q1213.” Science 265.5181 (1995): 2088-2090.

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Alpha-fetoprotein Screening for Fetuses with Neural Tube Defects: A Comparative Analysis of its Rise in Europe and America Danny Mammo Duke University When it comes to health care innovation, Americans are usually keen on medical innovation and novel technologies. When it came to alpha-fetaprotein (AFP) screening, however, the breakthrough did not receive the ready acceptance that one would expect in America. AFP, a protein produced by the fetus, tends to appear in elevated levels in the mother’s bloodstream if a neural tube defect is present, and depending on the age of the fetus the elevated levels may indicate future problems. While America resisted AFP screening, England and other parts of Europe began utilizing it nearly a decade earlier. While legitimate questions surrounded AFP screening with regards to its invasiveness and common misinterpretations, one must wonder why Europeans were much more readily accepting of AFP screening when they were surely faced with the same ethical dilemmas as American doctors and patients. To investigate this question, this paper will examine the cultural and social environments of Europe and America throughout the 1960’s and 1980’s. In a land of considerable commercialism and competitiveness generally and within the health care system particularly, Americans love the “imminent breakthrough.”1 As Keith Wailoo and Stephen Pemberton emphasize in the troubled dream of genetic medicine “the rise of a…therapeutic revolution has always had its allure.”2 This paper will examine a technology geared to better lives since its inception: alpha-fetoprotein (AFP) screening. AFP screening measures the amount of alpha-fetoprotein in the mother’s blood during her pregnancy; itt can help detect abnormalities in the infant, such as Down Syndrome. Oddly, AFP screening was not a target of America’s rush to accept the “imminent breakthrough” such as gene therapy for cystic fibrosis or bone marrow transplantation for sickle cell disease in the 1990s; rather, in an unusual turn of events, Americans were not readily accepting of another novel technology. Considering Americans’ keen liking to new medical technologies that promise a better lifestyle, why did America resist AFP screening for a decade while England and other parts of Europe began utiliz1 Wailoo, Keith and Pemberton, Stephen. The Troubled Dream of Genetic Medicine. Baltimore: Johns Hopkins UP, 2006. 2 Ibid.

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ing it during the 1970’s? In the late 1970’s the prospect of AFP screening for neural tube defects excited American researchers. Not until 1985, however, did AFP screening become a widespread option for physicians to offer to pregnant women.3 The lag in acceptance in America for AFP screening from 1975 to 1985 is often attributed to the screening’s prematurity, common misinterpretation of the tests, and the uncomfortable nature and invasiveness inflicted on women taking the test.4 While these attributions seem plausible, and surely affected America’s delayed acceptance of the screening, one must wonder whether these worrisome aspects of AFP screening were also present in Europe. Much of the research concerning AFP screening stemmed from the United Kingdom and France.5,6 If Americans were not unaware of the downsides of the innovative AFP screening, then should not Europeans have also been aware of the risks? I will try to illuminate the downsides and fears Americans and the F.D.A had of AFP screening while simultaneously highlighting parallel fears in Europe. If Europe then did face the same scientific and personal dilemmas as America, why did they much more readily accept AFP screening? To understand this dilemma one must examine the cultural and social environments in Europe and America throughout the 1960’s to 1980’s. In a new modern era of health reform for personalized medicine and a spike in the use of new, predictive medical technologies it is particularly vital to realize how various new medical breakthroughs are implemented geographically and their reasons for implementation. What other forces besides scientific influences affect a technology’s implementation? Why did AFP screening ultimately become pervasive in America 10 years after it had in Europe? If cultural and social factors did play a major part in America’s delay to accept the screening, did these factors suddenly vanish around 1985? If not, then why did many pregnant American women accept AFP screening post-mid 1980’s? AFP is a plasma protein produced by the baby’s liver and can be found in the mother’s blood. AFP screening involves a non-invasive, simple 3 Steinbrook, R. In California, Voluntary Mass Prenatal Screening. The Hastings Center Report, Vol. 16, No. 5. Oct. 1986, pp. 5-7. 4 Ibid. 5 Ruoslahti, E. Isolation and Biochemical Properties of Alpha-Fetoprotein. Prevention of Neural Tube Defects: The Role of Alpha-fetoprotein. Academic Press. 1978, pp. 9-16. 6 Brock, D. Prenatal Diagnosis of Neural Tube Defects Through Amniotic Fluid Measurements. Prevention of Neural Tube Defects: The Role of Alpha-fetoprotein. Academic Press. 1978, pp. 155-161.

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blood test taken between the 16th and 18th week of pregnancy.7,8 High levels of the fetal protein are warning signs for a neural tube defect. If the neural tube of the fetus has not closed appropriately, abnormal amounts of AFP are released into the amniotic fluid and subsequently, the mother’s bloodstream. If doctors detect an abnormal amount of AFP, they usually recommend a repeat test, and another positive result leads to an ultrasound examination examining for neural tube defects. To determine if the fluid surrounding the fetus contains abnormal AFP levels, an amniocentesis is then administered (Brody). In 1984, Dr. Irwin R. Merkatz noticed that low levels of AFP may indicate the presence of Down Syndrome.9 Today, AFP screening largely tests for neural tube defects (primarily spina bifida and anencephaly) and Down syndrome. I will focus on the use of AFP screening to detect for neural tube defects, because all of the early AFP research centered on screening for neural tube defects. In 1972, Scottish researchers, Drs. David Brock and Roger Sutcliffe, pioneered AFP screening. Even in their preliminary studies, significant pitfalls and limitations existed for AFP screening.10,11,12 Many false-positives were administered, and Brock attributed these readings to samples contaminated with fetal blood.13 Brock acknowledged the lack of a true standard for what range of AFP levels constituted abnormal or normal levels.14 To Brock, however, as we will see later, these causes for concern did not diminish his hope, or the hopes of other European physicians, for pregnant women to be screened for abnormal fetuses. In the early 1970’s, other research, including those conducted in the U.S., found further limitations to AFP screening. Aubrey Milunsky from the Department of Pediatrics at Harvard Medical School performed a study with 6500 cases and actually obtained a false positive rate of less than .1%.15 7 Ruoslahti, E. 8 Kolata, Gina. “Tests of Fetuses Rise Sharply Amid Doubts.” New York Times 22 Sept. 1987. 16 Nov. 2007 <www.nytimes.com>. 9 Ibid. 10 Brock, D. Prenatal Diagnosis of Neural Tube Defects Through Amniotic Fluid Measurements. Prevention of Neural Tube Defects: The Role of Alpha-fetoprotein. Academic Press. 1978, pp. 155-161. 11 Brock, D.J.H., and Scrimgeour, J.B., Early prenatal diagnosis of anencephaly. Lancet, 1972, 2: 1252-1253. 12 Brock, D.J.H., and Sutcliffe, R.G., Alpha-fetoprotein in the antenatal diagnosis of anencephaly and spina bifida. Lancet, 1972, 2: 197-199. 13 Brock, D.J.H., The molecular nature of alpha-fetoprotein in anencephaly and spina bifida. Clin. Chim. Acta, 1974, 57:315-320. 14 Brock, D. Prenatal Diagnosis of Neural Tube Defects Through Amniotic Fluid Measurements. Prevention of Neural Tube Defects: The Role of Alpha-fetoprotein. Academic Press. 1978, pp. 155-161. 15 Milunsky, A. Prenatal Detection of Neural Tube Defects: Experience with Alphafetoprotein Assays of Amniotic Fluid. Prevention of Neural Tube Defects: The Role of Alphafetoprotein. Academic Press. 1978, pp. 163-167

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Brock and Sutcliffe could never brag about finding such positive findings for AFP screening, yet Milunsky still found reservations to using AFP screening and duly noted them at the end of her study. Milunsky worried that doctors still did not realize that fetal blood contamination would lead to inaccurate readings. She was most worried by the fact that “the frequency of bloody amniocentesis” would be much too high, noting that ultrasounds should be the standard practice following an abnormal AFP reading.16 Unlike Brock and Sutcliffe, however, Milunsky emphasized that values from one laboratory should not be established as control values elsewhere, noting that values may differ with populations.17 If an American researcher obtained such a small false positive rate with an American population, why were Americans wary of AFP screening in comparison to Europeans? Considering the research findings, clinicians and policy makers in, both Europe and America, should have been wary of screening the general public because sufficient studies indicated that negative consequences of the screening still existed. In fact, Lorrin Lau and Susan Linkins of Johns Hopkins University performed a ground breaking study in 1976 establishing the best way to replace the normal range of AFP values by taking into account a geographic region’s normal population and abnormal population.18 Given Lau’s and Linkins’ new study and Milunsky’s nominal false positive rates, it would seem reasonable a priori for Americans to have been just as receptive to AFP screening as Europeans. If limitations and pitfalls to AFP screening were consistent in both cultures what, then, accounted for AFP screening’s late arrival to physicians’ clinics? The answer lies in the economic structure of England, other European countries, and America at the time. Just as important are the social and cultural values among the two different populations. We will see how certain ethical values taken for granted and accepted in one culture, can easily be unsolicited in another with respect to AFP screening. Reverend Hubert Hoskins in a 1968 London Times article titled Ambiguous Phenomenon of Religion in Decline admitted how “religious authorities no longer have a powerful hold over the mores of a society or on its politics and public life.”19 In Spain during the last days of the Franco regime, Catholic influence over Spaniards started to decline since the 1970’s. The death of Francisco Franco who had pronounced ties with the church led

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to the legalization of abortion and divorce in the 1980’s. Franco’s decline brought about a Socialist government and a secularist vibe in Spain during the 1970’s. Consumerism found its way into the Spanish public and many Spanish church leaders today believe that the rise of consumerism allowed the anti-clericalism always so prevalent in the Spanish left to become more pronounced.20 In America, religious curiosity was thriving from the 1960’s to 21 1980’s. Perhaps due to the Vietnam War from 1965 to 1975 and a need for support in a time of much irresponsible loss of life, religion was making headlines during these decades. In 1967, the University of Virginia, opened a religion department due to the curiosity spreading across the country, especially amongst the youth. Rutgers University reported a vast increase in the number of students taking religion courses. In the early 1980’s up to 1,100 students a semester were enrolled in a religion course at Rutgers.22 What can explain the disparity of religious zeal in Europe and America? How did the religious values of the two societies shape the acceptance or rejection of AFP screening in Europe and America? Many possible explanations can exist for religion’s decline in Europe and its power in America. Many immigrants living in America arrived after escaping Europe from religious oppression.23 Though this migrating trend has been constant in American history the rate increased in the 1950’s and 1960’s when the number of immigrants to the United States broke one million as 5,713,017 immigrants came to the United States during these decades. A majority of these immigrants arrived from Europe. Probably the most influential cause for an influx of European immigrants to America came during the failed 1956 Hungarian Revolution. Though the Soviets eventually crushed the Hungarian uprising, a transient hole in the Iron Curtain was created, allowing 447,000 Germans, 185,000 Italians, 52,000 Dutch, and 203,000 UK citizens to flee to America.24 For this reason, Americans may have felt closer to their religion and less likely to let go than Europeans. Secularization may have also been more prominent in Europe since the U.S. had a much more conservative government in the latter portions of the 1990s. From 1969 to 1989, three of the four presidents belonged to the

16 Ibid. 17 Ibid. 18 Lau, H. Lorrin, and Linkins, E. Susan. Pitfalls and Problems in the Interpretation of AFP Data- Myths and Misuse of the “Normal Range”. Prevention of Neural Tube Defects: The Role of Alpha-fetoprotein. Academic Press. 1978, pp. 221-233. 19 Huskins, Rev. Hubert. “Ambiguous Phenomenon of Religion in Decline.” The London Times 27 Jan. 1968. Times Digital Archive. Duke University Libraries. 18 Nov. 2007.

20 Loewenberg, Samuel. “As Spaniards Lose Their Religion, Church Leaders Struggle to Hold On.” New York Times 26 June 2005. 16 Nov. 2007 <www.nytimes.com>. 21 Maeroff, Gene I. “Religion Studies are Thriving.” New York Times 23 Oct. 1984. ProQuest. 16 Nov. 2007. 22 Ibid. 23 Lüchau, Peter. Report on Surveys of Religion in Europe and the United States. University of Copenhagen. 2004. 24 Békés, Csaba, and János Rainer. The 1956 Hungarian Revolution: a History in Documents. Budapest: Central European UP, 2002.

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Republican Party (Richard Nixon, Gerald Ford, and Ronald Reagan) with Democrat, Jimmy Carter, taking over from 1977 to 1981. The primarily politically conservative government may have influenced broader support for the churches. When the Supreme Court decided Roe v. Wade in 1973 and abortions were permissible widespread debates and controversies spread throughout the country. The last technology arriving in America in the 1970’s was a pre-natal screening which had influenced termination in Europe. With the 1976 Hyde Amendment restricting federal funding for abortion and spurring debates among feminists and others believing in woman’s choice and many on the religious right having pro-life stances, Americans were at a more entrenched divide than Europeans (Harris v. McRae). While nuances exist between the European countries, differences in religious zeal between Europe as a whole and America are clear. The divergent values accompanying the two populations affected the influence of researchers on the mainstream public with respect to accepting AFP screening. After Brock and Sutcliffe’s groundbreaking 1972 study in which they noted the lack of a true standard for abnormal or normal AFP levels, maternal serum was being used in Europe by 1974 to clinically detect AFP levels associated with neural tube defects. From 1972, the idea of terminating a pregnancy was spoken of by Brock, Sutcliffe and many other European researchers throughout the decade.25 The idea that almost immediately after AFP screening was discovered there was an expected connection between an abnormal fetus and termination may trouble many. The ethos in Europe, however, seems to suggest the contrary. In a culture where religion mattered less in the political realm and where its impact on lifestyle was slowly declining, Europeans seemed to have minimal objection to the link between abnormality and termination created by researchers. Brock and Sutcliffe, in the same year as their AFP studies of 1972, described their view of the promise that AFP screening brings: “A marker molecule, which indicates an affected fetus early enough to allow termination of pregnancy, has so far not been found. We suggest that AFP could act as such a marker molecule.”26 From finding a molecule to differentiate between abnormal and normal 25 Bishop JP, and Gagen, WJ. Ethics, justification and the prevention of spina bifida. J. Med. Ethics 2007; 33: 501-507. 26 Ibid.

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fetuses, Brock and Sutcliffe, themselves, made the abrupt jump and link to termination. Brock and Sutcliffe’s prematurity raises startling questions as to how much power and influence medicine should have. Even more troubling is the European reaction to such statements from AFP screening’s first development and use in clinical practice. With the Abortion Act of 1967 having passed in the U.K. legalizing abortion up to 28 weeks gestation, little or no discussion seemed to arise about the options provided by practitioners after a positive AFP screen for neural tube defects.27 Stuart Campbell, the Head of Obstetrics and Gynecology at St. George Hospital Medical School in London, performed a series of three case studies and all three cases resulted in the recommendation, rather than the alternative, of termination.28 In one of the case studies the subsequent ultrasound to the AFP screening resulted in no evidence of any neural tube defects, yet termination was still performed. The failure to separate abnormality from termination was not a rare circumstance among scientific circles in Europe during the 1970’s and 1980’s.29 In Leek et al, a London-based study, excitement was portrayed in 1974 as “the first reported case of prospective diagnosis and termination of an open neural tube defect [arose] from routine screening.”30 In a widely discussed paper in 1973 regarding “selective non-treatment,” English researcher John Lorber strongly advocated the termination of an infant with spina bifida, labeling the infant “too disabled to live.”31,32 While minimal objection existed among Europeans with regards to the link between abnormality and termination, opposition to AFP screening and the rush to terminate abnormal fetuses did exist. R.B. Zachary assertively promoted treatment of those with spina bifida.33 He and Lorber constantly debated the most efficient way to deal with abnormal fetuses. In a more secular Europe than America what made the views of Lorber, Leek, Campbell, and Brock so much more pronounced than those like Zachary? While Europeans began to evade religion, Europe could still not be labeled as secular. The economic influence in Europe, however, allowed for the majority’s voice to mask itself as the only voice. For similar economic reasons, the 27 Ibid. 28 Campbell S, Pryse-Davis J, Colart TM, et al. Ultrasound in the diagnosis of spina bifida. Lancet 1975; 7915: 1065-1068. 29 Bishop JP, and Gagen, WJ. 30 Leek AE, Leghton AH, Kitau MU, et al. Prospective diagnosis of spina bifida. Lancet 1974; 7895: 1551. 31 Lorber J. Early Results of selective treatment of spina bifida. Lancet 1973; 5886: 201204. 32 Lorber J. Commentary one and reply to John Harris. J Med Ethics 1981; 7: 120-122. 33 Zachary RB. Ethical and social aspects of treatment of spina bifida. Lancet 1968; 7565: 457.

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American public was more responsive than the Europeans to the reservations and limitations expressed by Milunsky, Lau, and Linkins over AFP screening. Many decisions stem from the theory of cost-effectiveness and the acceptance of AFP screening is no exception. Economist Arnold Kling’s Crisis of Abundance emphasizes the idea that new, expensive technologies have caused a dramatic spike in health care costs. In systems with social medicine, like many nations in Europe, this problem does not exist since the government paying for health care refuses to use new, expensive technology or restricts its’ widespread use. Kling compares the American system to socialist systems, noting that “Heart bypass surgery is about three times as prevalent [in the US] as in France and about twice [as in the U.K]. Angioplasty is more than twice as prevalent…as in France and about seven times as [in the U.K].”34 In Europe, as governments spends less on health care, the government would surely favor the prospect of terminating abnormal fetuses with neural tube defects rather than using resources on costly treatments. Sure enough, the governments in Europe began promoting termination in subtle ways. The U.K.’s National Health Service (NHS), created in 1948, was reorganized in 1974 in order to “[reorient behavior] to keep people healthy and to improve the quality of life.”35,36 Brock, Campbell, Lee, and Lorber all had the government’s support in promoting AFP screening with the implied link of termination and abnormality. In a final landmark study aimed at putting together all of the findings, the 1977 UK Collaborative Study offered termination as “the only means available for reducing the number of live infants born with…defects” (UK Collaborative Studies, 1323-1332). Again, termination was seen as a recommendation, rather than an alternative. Others like RJ Brereton and Walker were against the link made between termination and abnormality, and letters were sent to the Lancet.37,38 However, “the question of decision making remained unworthy of lengthy discussion.”39,40 In a startling finish to the European AFP screening situation, the 34 Kling, Arnold. Crisis of Abundance. Cato Institute, 2006. 35 Baggot R. Public health policy and politics. Basingstoke: Macmillan, 2000. 36 Deparment of Health and Social Security, Department of Education and Science Scottish Office and Welsh Office. Prevention and health. London: HMSO, 1977 (Cmnd, 7047). 37 Brereton RJ, Cudmore RE, Irving IM, et al. Screenning for neural-tube defects. Lancet 1978; 8069: 879. 38 Walker J. Ethical problems of screening for neural-tube defects. Lancet 1978; 8085: 373. 39 Laurence KM. Fetal malformations and abnormalities. Lancet 1974; 7886: 939-941. 40 Brock DH. Screening for neural tube defects. In: Srimgeour JB, ed. Towards the prevention of fetal malformation. Edinburgh: Edinburgh University Press, 1978:37-46.

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U.K.’s Department of Health and Social Security (DHSS) actually acknowledged that many of the views expressed regarding AFP screening may not be humanitarian. In a 1970’s DHSS document the opening paragraph states that, “While the humanitarian arguments for the prevention of spina bifida… are paramount, the economic considerations also deserve examination.”41 Juxtaposing the humanitarian and the economic, this DHSS document emphasizes how Europe, and especially the UK, accepted AFP screening so readily. The push by the government, backed by economic incentives, faced almost no resistance as the humanitarian aspect of linking termination and abnormality had less of a voice while religion’s influence slowly declined among the people. In America, on the other hand, Lyndon B. Johnson’s presidency in the 1960’s brought about his “Great Society” dream and the federal government’s spending increased significantly for health care programs (ex. Medicare), food stamps, and many grants to schools and colleges for improved education. In the early 1970’s, however, the war in Vietnam led to stagflation (The U.S. Economy: A Brief History). As a desperation ploy, President Carter from 1977-1981, continued to increase government spending as his way to fix the economy’s weakness and the unemployment problems. With high government spending and a system where individuals, pharmaceutical, and insurance companies contribute to paying for health care, America had the resources to listen to Americans Milunsky, Lau, and Linkins and work on improving the limitations expressed about AFP screening. In 1982, however, America underwent a deep recession as the number of businesses going bankrupt rose 50%.42 Could the recession have played a role in America finally implementing AFP screening as a widespread tool? The actions by the American College of Obstetricians and Gynecologists (ACOG) suggest so. Like when Europe had fewer resources to treat abnormal fetuses, shortly after the recession in 1984 and 1985 the ACOG advised American physicians that lawsuits would surely follow if the AFP test was not offered to children. It is important to note that prior to 1985 doctors may have refused screening pregnant women for AFP levels not only because of ethical dilemmas due to religious arguments. Instead, as shown, the economic capabilities of a government powerfully influenced whether practitioners heeded the advice of researchers underscoring limitations to the technology. And 41 Department of Health and Social Security. Screening for spina bifida and other neural tube defects. Royal College of Obstetricians and Gynecologists Archive, Working Group on Screening for Neural Tube Defects, 1973-1979, College Presidents’ Records, 1977-1981. 42 “The U.S Economy: a Brief History.” Outline of the U.S Economy. 17 Nov. 2007 <usinfo.state.gov>.

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if forces besides medical dilemmas (as this paper describes) factored into the delay of America’s acceptance of AFP screening why, then, did pregnant Americans readily take up the test post-1985? Did religious and cultural factors suddenly change in America? Such a radical shift seems highly unlikely. Abortion debates still rage on today. The economic factors, on the other hand, did change. The story of AFP screening offers an important lesson for the future of American medicine, manifesting the likelihood that after a test is offered to the mainstream public, Americans will most likely bite into the “allure…of a therapeutic revolution” (Wailoo & Pemberton, 171). As new tests unfold with ethical implications will America’s desire for the imminent breakthrough always win out? How much do ethical dilemmas truly matter once a test is supported by the government or other influential businesses? Similar ethical dilemmas in the AFP debate prior to 1985 had just as much credibility post-1985. Will ethical arguments be left to constant debate while powerful proponents of new technologies push them to the market? Ethical dilemmas prolonged the emergence of AFP screening in America as seen in the AFP story but once the government promulgated the screening and doctors were forced to do so by the ACOG the competitiveness and commercialism that defines American people emerged as many women accepted AFP screening. The story of AFP screening sheds light on the influence economic forces and powerful corporations like the ACOG, NHS, and DHSS have on controlling the propagation of new technologies. Pharmaceutical companies and other powerful corporations must heed Americans willingness to accept a technology once it is placed on the market. Unfortunately our economic reward system does not compensate for such concern and a novel era of constantly new diagnostic tools must lead us to question corporations looking to impetuously push new technologies. Americans must be aware of current technological developments and resolutely voice any opinions raising ethical arguments prior to the technology’s dissemination. As seen with AFP screening the delay of a new technology geared to change lives is possible.

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Works Cited Baggot R. Public health policy and politics. Basingstoke: Macmillan, 2000. Békés, Csaba, and János Rainer. The 1956 Hungarian Revolution: a History in Documents. Budapest: Central European UP, 2002. Bishop JP, and Gagen, WJ. Ethics, justification and the prevention of spina bifida. J. Med. Ethics 2007; 33: 501-507. Brereton RJ, Cudmore RE, Irving IM, et al. Screenning for neural-tube defects. Lancet 1978; 8069: 879. Brock, D.J.H., and Scrimgeour, J.B., Early prenatal diagnosis of anencephaly. Lancet, 1972, 2: 1252-1253. Brock, D.J.H., and Sutcliffe, R.G., Alpha-fetoprotein in the antenatal diagnosis of anencephaly and spina bifida. Lancet, 1972, 2: 197-199. Brock, D.J.H., The molecular nature of alpha-fetoprotein in anencephaly and spina bifida. Clin. Chim. Acta, 1974, 57:315-320. Brock DJH. Screening for neural tube defects. In: Srimgeour JB, ed. Towards the prevention of fetal malformation. Edinburgh: Edinburgh University Press, 1978:37-46. Brock, D. Prenatal Diagnosis of Neural Tube Defects Through Amniotic Fluid Measurements. Prevention of Neural Tube Defects: The Role of Alpha-fetoprotein. Academic Press. 1978, pp. 155-161. Brody, Jane E. “Health; Personal Health.” New York Times 20 July 1989. 16 Nov. 2007 <www.nytimes.com>. Campbell S, Pryse-Davis J, Colart TM, et al. Ultrasound in the diagnosis of spina bifida. Lancet 1975; 7915: 1065-1068.

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Deparment of Health and Social Security, Department of Education and Science Scottish Office and Welsh Office. Prevention and health. London: HMSO, 1977 (Cmnd, 7047). Department of Health and Social Security. Screening for spina bifida and other neural tube defects. Royal College of Obstetricians and Gynecologists Archive, Working Group on Screening for Neural Tube Defects, 1973-1979, College Presidents’ Records, 1977-1981. Harris v. McRae, 448 U.S. 297 (1980). Findlaw.com. 17 Nov. 2007. Huskins, Rev. Hubert. “Ambiguous Phenomenon of Religion in Decline.” The London Times 27 Jan. 1968. Times Digital Archive. Duke University Libraries. 18 Nov. 2007. Kling, Arnold. Crisis of Abundance. Cato Institute, 2006. Kolata, Gina. “Tests of Fetuses Rise Sharply Amid Doubts.” New York Times 22 Sept. 1987. 16 Nov. 2007 <www.nytimes.com>. Lau, H. Lorrin, and Linkins, E. Susan. Pitfalls and Problems in the Interpretation of AFP Data- Myths and Misuse of the “Normal Range”. Prevention of Neural Tube Defects: The Role of Alpha-fetoprotein. Academic Press. 1978, pp. 221-233. Laurence KM. Fetal malformations and abnormalities. Lancet 1974; 7886: 939-941. Leek AE, Leghton AH, Kitau MU, et al. Prospective �� diagnosis of spina bifida. Lancet 1974; 7895: 1551. Loewenberg, Samuel. “As Spaniards Lose Their Religion, Church Leaders Struggle to Hold On.” New York Times 26 June 2005. 16 Nov. 2007 <www.nytimes.com>. Lorber J. Early Results of selective treatment of spina bifida. Lancet 1973; 5886: 201-204. 28

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Lorber J. Commentary one and reply to John Harris. J Med Ethics 1981; 7: 120-122. Lüchau, Peter. Report on Surveys of Religion in Europe and the United States. University of Copenhagen. 2004. Maeroff, Gene I. “Religion Studies are Thriving.” New York Times 23 Oct. 1984. ProQuest. 16 Nov. 2007. Milunsky, A. Prenatal Detection of Neural Tube Defects: Experience with Alpha-fetoprotein Assays of Amniotic Fluid. Prevention of Neural Tube Defects: The Role of Alpha-fetoprotein. Academic Press. 1978, pp. 163-167. Ruoslahti, E. Isolation and Biochemical Properties of Alpha-Fetoprotein. Prevention of Neural Tube Defects: The Role of Alpha-fetoprotein. Academic Press. 1978, pp. 9-16. Steinbrook, R. In California, Voluntary Mass Prenatal Screening. The Hastings Center Report, Vol. 16, No. 5. Oct. 1986, pp. 5-7. “The U.S Economy: a Brief History.” Outline of the U.S Economy. 17 Nov. 2007 <usinfo.state.gov>. UK Collaborative Study on Alpha-fetoprotein in Relation to Nerual-tube Defects. Maternal Serum alpha-fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Lancet 1977; 8026: 1323-1332. Wailoo, Keith, and Stephen Pemberton. The Troubled Dream of Genetic Medicine. Baltimore: Johns Hopkins UP, 2006. Walker J. Ethical problems of screening for neural-tube defects. Lancet 1978; 8085: 373. Zachary RB. Ethical and social aspects of treatment of spina bifida. Lancet 1968; 7565: 457. 29

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The Ethics of Egg Donation Jacquelyn Hatch Brown University Advanced reproductive technologies today allow the harvesting of eggs from one woman, the fertilization of those eggs, and then the implantation of those eggs into another woman. Currently one of the only ways that a person desiring human eggs can obtain them is through the process of egg donation. Every day across the country newspapers publish advertisements targeting mainly college aged females requesting women interested in donating their eggs. Though seemingly a quick and easy way to make large sums of money, many are unaware of the ethical questions that should be considered when contemplating egg donation. While considered by many to be one of the best options for women unable to naturally conceive a child, the way in which the system of egg donation currently functions in the United States raises many ethical concerns. Such issues include the conflicting roles a physician must play in the process of egg donation, issues with informed consent, and the presence of coercion in donor compensation. Advertisements often target vulnerable populations that might not fully understand the implications of their actions. Do to these concerns and more, the system of egg donation as it exists today in our country is an unethical one that needs to be reformed. Seventy-five thousand dollars is given as a reward for helping out an unfortunate couple for giving them something you weren’t even going to use, something that they will cherish for the rest of their lives. It seems too good to be true. But every day, female university students are inundated with advertisements that offer them huge sums of money for one little thing: an oocyte, an ovum, an egg. Anyway you put it, infertile couples want it. In today’s world of growing reproductive technologies, even people whose bodies don’t allow them to reproduce normally can have their own children. For those women who can carry fetuses but are not able to produce their own eggs, the answer is egg donation through in vitro fertilization. Other women “donate” their eggs and then are compensated for their troubles. It all seems simple enough. But yet, if it were really this easy, wouldn’t we all be doing it? Why do couples have such trouble finding donors? The problem is that the system of egg donation in our country today is not so clear cut and simple. There are troubling underlying ethical questions that 30

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arise. Is it right to sell part of the body? How far does the right to reproduce extend? The whole system seems to run on a strange kind of commercialism, one that uses cells of the human body to turn a profit, and doesn’t legally exist anywhere else in our nation’s healthcare system.1 The infertile couples who receive these eggs truly feel themselves to be in need, but that does not mean that they should be able to take part in a process like egg donation that has so many ethical problems. Because of the conflicting roles a physician must play in the process of egg donation, issues with informed consent, and the presence of coercion in donor compensation, among other problems, the practice of egg donation as it exists in the United States today is an unethical one that needs to be reformed. One of the greatest issues that the physician must face when he takes part in egg donation concerns his relationships with both the patients. Even though it might not seem like it, the infertile woman is not the physician’s only patient in this scenario. The donor is also taken under the care of the physician, and so he is responsible for her as well. She must undergo an initial health screening, receive multiple medications via injection, and eventually undergo surgical removal of the eggs. Since both the donor and the recipient are the physician’s patients, he is confronted with a great conflict of interest. The recipient is the original patient of the physician, and so he may feel a stronger duty toward her. The physician could also have a harder time creating a comfortable doctor/patient relationship with the donor, since she is not there for her own health reasons, but only to make money.2 The high probability that the recipient will have more money than the donor could cause him to favor the donor. This is especially true since the success and reputation of his practice relies mostly on the happiness of the recipient with the outcome, and not the donor. Even though the physician should treat each of these patients with equal care, problems arise when the care each needs conflict completely. Since it has been shown that the more eggs doctors have to work with, the greater the chance of successful IVF, the recipient needs as many eggs harvested as possible for a positive outcome.3 But the more eggs that are taken from the donor, the more at risk she is for possible complications, such as 1 Kahn, Jeffrey. “Can We Broker Eggs Without Making Omelets?” American Journal of Bioethics 1 (2001): 14-15. 2 Nisker, Jeffrey A. “Physician Obligation in Oocyte Procurement.” American Journal of Bioethics 1 (2001): 22-23. 3 Advanced Fertility Center of Chicago. “IVF Success Rates by Number of Eggs and Female Age, Egg Quality & Quantity Problems.” Advanced Fertility Center of Chicago Infertility & IVF Specialists. 20 Mar. 2009 <http://www.advancedfertility.com/eggspregnancyrates. htm>.

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ovarian hyperstimulation syndrome, which may even require hospital admission.4 The physician must be careful to balance between an overly cautious approach and excessive stimulation.5 If he takes too many, he is not looking out for the donor’s well-being, but if he doesn’t take enough, he is not acting in the best interest of the recipient. The current system of egg donation does not give the doctor a magic number of eggs to take from one patient and give to another. He must use his best judgment to fairly balance the needs of each of these women. Since it is almost impossible to do the best work for both patients, the physician is forced into an unethical role in which he must favor one patient over another. Another issue that arises when dealing with egg donations is the extreme lack of informed consent that donors are presented with. Their initial introduction to the process is usually through print ads in newspapers (often college newspapers), magazines, or flyers that highlight the large sums of money to be given out, but do not mention any possible consequences or side effects from the procedures. This misleads the donors and does not allow them to make an initial informed or voluntary decision. Gurmankin’s study of donor recruiters that conducted preliminary phone interviews with women interested in donating showed that the majority of donor programs do not provide accurate or complete information of the risks associated with egg donation.6 It has also been found that many patients assume that because it is a process accepted by a physician, there must be nothing particularly dangerous about egg donation.7 The procedure the donor must undergo, though, is very serious and has some dangerous possible consequences, including pain, excessive stimulation of the ovaries, bleeding, and infection.8 Since physicians strive to follow the “do no harm” principle, donors assume they shouldn’t worry about the risks they are facing. In his commentary of a case example of egg donation, Lee argues against this claim by saying that the public does not necessarily accept all health risks without question simply because a physician is part of the equation. He claims that there are many easily accessible ways for patients to educate themselves about risks, including the internet,

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and that even if patients still fully trust in the physician’s approval of the process, that they will still be informed of all the risks later on.9 But this assumes that the donors will be given all the proper information, which Gurmankin proved they often aren’t. There is also evidence in her study that shows that many donors who are presented with risk information do not completely understand what they are being told.10 Even when adequate information is presented to the donor, it can often be overshadowed by the incredible amounts of money offered to the donors, who are much of the time financially struggling university students. Advertisements give details of what students may do with the money, such as paying for student loans, grad school tuition, or study abroad, which to a student, all seem incredibly appealing.11 The inconvenience and discomfort of the procedure may seem like nothing compared to what money they have to gain. Even though the process of egg donation has existed now in the United States for more than twenty years, there are a limited number of studies that have examined the long term consequences for donors. Even fewer studies have considered the possible emotional and psychological impact on donors.12 One small study that did survey previous egg donors found only 35% said that they would be willing to go through the process again.13 It is possible then that some of the most devastating consequences may not even be fully realized. It must be recognized that even if the donor at first believes she is happier after the process, at some point in her life she may be hit by the psychological consequences of knowing that somewhere in the world there is a baby who is genetically her child. Even though this may not affect everyone, these consequences have the possibility of doing great damage to a woman, especially if for some reason she never has a child of her own. Even if the patient doesn’t fully understand the risks, the physician definitely should. He should be able to understand that the risks can be quite extreme, and obviously, for the donor, not medically necessary. Medical risks are usually only acceptable in order to save or improve the quality or length

4 Bodri, Daniel, Juan Jose Guillen, Ana Polo, Marta Trullenque, Carolina Esteve, and Oriol Coll. “Complications related to ovarian stimulation and oocyte retrieval in 4052 oocyte donor cycles.” Reproductive BioMedicine Online 17 (2008): 237-43. 5 Mastroianni Jr., Luigi. “Risk Evaluation and Informed Consent for Ovum Donation: A Clinical Perspective.” American Journal of Bioethics 1 (2001): 28-29. 6 Gurmankin, A. D. “Risk information provided to prospective oocyte donors in a preliminary phone call.” American Journal of Bioethics 1 (2001): 3-13. 7 Lee, Peter H. “Commentary on “Seventy Ova”” Hastings Center Report (July-Aug 2001): 14. 8 Mastroianni Jr., Luigi.

9 Lee, Peter H. 10 Gurmankin, AD. 11 Kay, Julia. “Women and egg at Brown.” The Brown Daily Herald [Providence] 27 Sept. 2004. 12 Schneider, Jennifer, and Wendy Kramer. “IVF News - Egg donors need long-term follow-up: Recommendations from a retrospective study of oocyte donors in the US.” IVF.net In vitro fertilization, Infertility, embryology and IVF News. 19 Jan. 2009. Progress Educational Trust. 20 Mar. 2009 <http://www.ivf.net/ivf/egg_donors_need_long_term_follow_up_recommendations_from_a_retrospective_study_of_oocyte_donors_in_the_us-o3950.html>. 13 Klock, Susan Caruso, Jan Elman Stout, and Marie Davidson. “Psychological characteristics and factors related to willingness to donate again among anonymous oocyte donors.” Fertility and Sterility 79 (Jun 2003): 1312-316.

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of the patient’s life.14 The only benefit to the donor here is monetary, while she undertakes serious medical risks. In his commentary Lee argues that the benefits to the donor are much greater than most people realize. The money could be a great improvement in the donor’s life, and while the donor receives such great benefits, the recipient is also getting the child she has wanted for so long. Both donor and recipient come out of the process with great rewards.15 But in the field of medicine, money should never be more important than the health and safety of a patient. The large sums of money given to the donors amount to bribes, not rewards, for undergoing a dangerous and painful process. Another argument against the line of reasoning that egg donation is unethical because it is an unnecessary risk to save or improve the patient’s life points out the fact that our society finds it not only perfectly ethical but also praiseworthy for someone to donate their organ to a relative or friend, even though there are also great risks with no chance of benefits to the donor in this case. But the actions of the organ donor here are for completely altruistic reasons. It would be a completely different case if egg donations were given willingly and without any form of compensation. And while many egg donors probably do have some altruistic motivations, it is hard for me to believe that the majority of egg donors were not originally attracted to the process because of the promise of a large sum of money. As the monetary offers increase in the advertisements, so do the potential levels of coercion. In other areas of healthcare, we strive to keep monetary offers from forcing people to ignore possible risks to their own health. Strict guidelines are followed by researchers, who are permitted only to pay their participants for expenses and a minimal amount as a reward or incentive. According to Grady in her commentary on money for research participation, “the amount of money offered through research participation should be standardized and calculated so that it is more or less comparable to that available through other similar unskilled moneymaking opportunities in the relevant community.”16 Any payment greater than this is considered unethical because it is a form of coercion. It incentivizes those who are at an economical disadvantage to take health risks because it appears to be a quick and easy way to make a large amount of money. In some poorer societies,

people are forced to sell their kidneys if they want to make money.17 This practice is illegal in the United States, but selling eggs for money is not. The high sums offered must influence women to donate eggs when otherwise they would not. A topic of counterargument that is at times used against this coercion line of reasoning in the egg donation debate is the idea of the autonomy of the donor. She has the right to decide what she wants to do with her eggs and her choices to do what she will with her eggs are her decisions that must be respected. She should also have the right to take any risks that are part of the process, and that decision should be left up to her. Some people even consider her eggs to be her “property” and so they are hers to give away or sell.18 It seems strange to me though to consider your own body as something that you own and are able to sell. While it is true that people sell “parts” of themselves all the time, such as their talents or physical beauty, I think that this situation is different. A woman’s eggs are not just pieces of a person’s body. They hold some intrinsic value, at least symbolically, of the life that they could create. And often it does not hold that a property rights model is the best way to describe a person or her body. It seems right to give a part of yourself for a “worthy and altruistic cause”, again like an organ donor giving to someone to prevent their death, but to sell yourself lowers the value of the human body and the eggs themselves. Again, it would be different if the egg donors were really giving away their eggs, but with rates in the thousands, or even higher for certain eggs, most of the money is going to pay for the actual eggs, and not the time the donor spends on the process. Since the 1984 National Organ Transplantation Act makes it illegal to sell human organs, and this mandate is usually extended to human tissues as well, women are not usually considered to be ‘selling’ eggs, but are considered instead to be ‘donating’ eggs, while being compensated for their ‘hardships.’ But sums today greatly surpass what would be equated with fair compensation, which should only include payment for time spent, as well as risks and burdens of the procedure.19 With such large amounts of money being offered, the donors are in effect selling their eggs. No other human tissues are bought and sold in such a commercialized system. Payments for the eggs have been driven up by a supply and demand market. The competitive recruitment that results and the lack of a third party reimbursements for

14 Jacobs, Allan. “Commentary on “Seventy Ova”” Hastings Center Report (July-Aug 2001): 13-14. 15 Lee, Peter H. 16 Grady, Christine. “Money for Research Participation: Does It Jeopardize Informed Consent?” American Journal of Bioethics 1 (Spring 2001): 40-44.

17 Jacobs, Allan. “Commentary on “Seventy Ova”” Hastings Center Report (July-Aug 2001): 13-14. 18 Blacksher, Erika. “On Ova Commerce.” Hastings Center Report 30 (Sept-Oct 2000): 29-30. 19 Sipes, D. “State, federal statutes guide organ donation procedures.” Health Progress 68 (1987): 46-50, 67.

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egg donations leads to an unfair system in which only the richest couples can afford to buy eggs.20 Kahn presents the argument that since egg donation and reproductive medicine in general do not constitute life saving medical care, then it could be considered reasonable for commercial markets to control who has access to the eggs.21 But is it fair and ethical for access to a scarce healthcare resource to be allocated based on the ability to pay? Beauchamp and Childress recognize that in the U.S. health care system services are commonly allocated based on a person’s ability to pay.22 They argue though that a just system would instead be based upon egalitarian standards, meaning a system that “emphasizes the equal worth of persons and fair opportunity.”23 A system that rewards those with money over all others is not considered to be fair and just. Since the rich and needy couples are offering so much money for the eggs, they have the power to only accept eggs that are from the most desirable donors. The market also only allows the “best” to donate their eggs and profit from it. Ads in Ivy League newspapers specify that donors have a certain SAT score, height, and weight, among other qualities that are deemed attractive, intelligent, and pleasing.24 Thus a system is created in which only the richest can buy the eggs, since they have to not only pay the fee of the donor but also the incredibly high medical bills that come from this process, and only the most genetically fortunate can donate them, leaving many other unfortunates out of the picture, on both sides of the story. The fact that the infertile families are actually “recruiting” the most intelligent and beautiful donors also brings up another ethical dilemma. The process begins to take on the traits of an expensive kind of eugenics experiment, in which parents are able to pay for exactly what kind of traits they desire in their children. The history of eugenics reminds us how easy it is for scientific “improvements” to be used for the wrong reasons, such as eliminating those people that society does not feel are fit, or by not allowing them to procreate.25 Attitudes of discrimination in society can be fueled when people begin to decide what the best traits are for their children. It is not right or permissible to attempt to choose the eye color or level of intelligence 20 Kahn, Jeffrey. 21 Ibid. 22 Beauchamp, Tom L., and James F. Childress. Principles of Biomedical Ethics. 5th ed. New York: Oxford UP, USA, 2001. 23 Ibid. 24 Kay, Julia. “Women and egg at Brown.” The Brown Daily Herald [Providence] 27 Sept. 2004. 25 Mitchell, C. Ben. “Eugenics in the Springtime.” The Center for Bioethics & Human Dignity. 2002. 20 Mar. 2009 <http://www.cbhd.org/resources/genetics/mitchell_2002-03-05. htm>.

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of “naturally” conceived children, so it does not seem right that parents can go about doing this by getting what they consider to be the perfect egg. Even when it comes to choosing something as simple as the gender of the future child, organizations such as the American Society of Reproductive Medicine state that in patients undergoing IVF, selecting for gender has the “risk of gender bias, harm to individuals and society, and inappropriateness in the use and allocation of limited medical resources.”26 On the other hand though, if parents want to obtain an egg to create a child, shouldn’t they be able to decide if the one they are paying for is ‘adequate’ or not? They should know if the donor has led an unhealthy lifestyle, or has a family history of genetic diseases. They should be able to choose an egg that has similar traits to their own, so that the child could still resemble the infertile parent. For those who believe that egg donation should be acceptable, the main argument is that all people have the right to reproduce. For many couples, conceiving, bearing, and rearing a child are all part of a central freedom that a free society should allow them to enjoy if possible. A mother may have the feeling that it is not “her” child unless she gives birth to it. Our society has a strong emphasis on biological relations being more important than social relations in the role of a parent. If we recognize the rights for a couple to produce a sexually conceived baby, then we should also recognize the rights of a couple that must have their baby another way. Someone who has an infertile partner should not be penalized because they chose to spend their life with someone who does not have the ability to reproduce. The fertile partner should still have a chance to have a biological child.27 But once again, the system of egg donation does not grant reproductive rights to all those who desire them. The way that the system is set up, it is not the infertile couples who are given the right to have children. It is the infertile couples who have money. If we grant all people the right to have children any way we please, we should again not limit couples based on how much money they have. There are also greater social implications here that we must take into consideration. The general acceptance of egg donation has the possibility of leading to detrimental effects on society’s views on the value and dignity of the human body, which could in turn lead to a society in which it is acceptable to sell human organs for profit. I believe that most people would agree 26 Merhi, Z. O., and L. Pal. “Gender “tailored” conceptions: should the option of embryo gender selection be available to infertile couples undergoing assisted reproductive technology?” Journal of Medical Ethics 34 (2008): 590-93. 27 Little, Margaret O. “Procreative Liberty, Biological Connections, and Motherhood.” Kennedy Institute of Ethics 6 (1996): 392-96.

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that a system that advocates selling human organs for profit could never be ethical or acceptable. As proof of this one would only need to take notice that such a system does not exist legally in our own country or in most countries across the world. A system of organ selling would no doubt result in the poorest dismissing their own health risks for profit, an occurrence previously demonstrated as unethical in this paper. This kind of system could also provide incentives for some of the more criminally minded to go to such lengths as murder to procure organs for profit. Egg donation and the extents to which we have developed reproductive technologies also seem unethical in terms of social justice. We devote so much money and resources to developing these technologies, when there are so many children in the world who could be adopted by these couples, and so many areas of medical research in which these resources could be used. Again, the entire process continues because of the market forces. There are people who are willing to pay for reproductive technologies, and so they will continue on. What I find especially unnerving about the process is the target audience that donor programs are attempting to exploit. Too often society assumes that there is no need to worry about the well being of college students when compared to other groups in society, since they are lucky enough to have opportunities for higher education and other positive aspects of college life. But the majority of college students have only recently begun living on their own. Up until college, these students have not had to make any important health or money related decisions on their own. Many are overwhelmed with the new freedoms that they have been granted, and do not know how to handle it all. The advertisements that solicit egg donors in college newspapers are going after a weakened audience. In such a vulnerable state, female college students could agree to the process of egg donation and sincerely regret it later, especially when the compensation funds run out. Though paying for a donated egg and being able to carry and deliver a baby may make infertile couples very happy, I do not think that the system of egg donation as it exists today in our country is an ethical one. It could lower the standard of practice of the participating physician, or force him into a confusing conflict of interest between two patients. Donors are usually wrongly coerced into the process and not given all the information right away, which does not allow them to make an informed decision about their participation. It is also a system that wrongly commercializes the human body and what it produces. I think that the best thing for infertile couples to

do would be to adopt a child, but if they are strongly against that, and really wish to carry a baby, then perhaps there are other systems that could be in place that would be more ethical. One way to resolve to conflict of interest that a physician is faced with when he deals with both the donor and the recipient is to have separate physicians for each of these patients, so that each physician is able to appropriately represent the best interests of his patient. This though does not solve any of the other numerous problems that accompany egg donation. Another system that was originally in place in the United States and is still used in Canada was a system of “sharing” that eliminated some of the conflict of interest problems and also the issue of coercion. The donors were women with damaged fallopian tubes, but no money to pay for in vitro fertilization (IVF). They gave half their eggs away in exchange for free IVF.28 Although I still think it would be better not to exchange the eggs for something desirable and there are still many other issues to consider with this method, it does appear to be slightly more ethically acceptable if there are no other considerations for the infertile couples. Unfortunately though, it seems that as the population of people desiring to reproduce grows older, there will be a greater demand for donated eggs. And a greater demand means an even greater commercialization of the system of egg donation.

28 Nisker, Jeffrey A. “Physician Obligation in Oocyte Procurement.” American Journal of Bioethics 1 (2001): 22-23.

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Works Cited Advanced Fertility Center of Chicago. “IVF Success Rates by Number of Eggs and Female Age, Egg Quality & Quantity Problems.” Advanced Fertility Center of Chicago Infertility & IVF Specialists. 20 Mar. 2009 <http://www.advancedfertility.com/eggspregnancyrates. htm>.

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Klock, Susan Caruso, Jan Elman Stout, and Marie Davidson. “Psychological characteristics and factors related to willingness to donate again among anonymous oocyte donors.” Fertility and Sterility 79 ( Jun 2003): 1312-316. Lee, Peter H. “Commentary on “Seventy Ova”” Hastings Center Report ( July-Aug 2001): 14.

Beauchamp, Tom L., and James F. Childress. Principles of Biomedical Ethics. 5th ed. New York: Oxford UP, USA, 2001.

Little, Margaret O. “Procreative Liberty, Biological Connections, and Motherhood.” Kennedy Institute of Ethics 6 (1996): 392-96.

Blacksher, Erika. “On Ova Commerce.” Hastings Center Report 30 (SeptOct 2000): 29-30.

Mastroianni Jr., Luigi. “Risk Evaluation and Informed Consent for Ovum Donation: A Clinical Perspective.” American Journal of Bioethics 1 (2001): 28-29.

Bodri, Daniel, Juan Jose Guillen, Ana Polo, Marta Trullenque, Carolina Esteve, and Oriol Coll. “Complications related to ovarian stimulation and oocyte retrieval in 4052 oocyte donor cycles.” Reproductive BioMedicine Online 17 (2008): 237-43. Grady, Christine. “Money for Research Participation: Does It Jeopardize Informed Consent?” American Journal of Bioethics 1 (Spring 2001): 40-44. Gurmankin, A. D. “Risk information provided to prospective oocyte donors in a preliminary phone call.” American Journal of Bioethics 1 (2001): 3-13. Jacobs, Allan. “Commentary on “Seventy Ova”” Hastings Center Report ( July-Aug 2001): 13-14. Kahn, Jeffrey. “Can We Broker Eggs Without Making Omelets?” American Journal of Bioethics 1 (2001): 14-15. Kay, Julia. “Women and egg at Brown.” The Brown Daily Herald [Providence] 27 Sept. 2004.

Merhi, Z. O., and L. Pal. “Gender “tailored” conceptions: should the option of embryo gender selection be available to infertile couples undergoing assisted reproductive technology?” Journal of Medical Ethics 34 (2008): 590-93. Mitchell, C. Ben. “Eugenics in the Springtime.” The Center for Bioethics & Human Dignity. 2002. 20 Mar. 2009 <http://www.cbhd.org/resources/genetics/mitchell_2002-03-05.htm>. Nisker, Jeffrey A. “Physician Obligation in Oocyte Procurement.” American Journal of Bioethics 1 (2001): 22-23. Schneider, Jennifer, and Wendy Kramer. “IVF News - Egg donors need longterm follow-up: Recommendations from a retrospective study of oocyte donors in the US.” IVF.net - In vitro fertilization, Infertility, embryology and IVF News. 19 Jan. 2009. Progress Educational Trust. 20 Mar. 2009 <http://www.ivf.net/ivf/egg_donors_need_ long_term_follow_up_recommendations_from_a_retrospective_ study_of_oocyte_donors_in_the_us-o3950.html>. Sipes, D. “State, federal statutes guide organ donation procedures.” Health Progress 68 (1987): 46-50, 67. 41

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Among the first principles of what we now call bioethics were those conceived in Pharonic Egypt. MAAT, the concept of truth, justice, righteousness, balance and order, dates to 4000-3500 BC. It calls for individual responsibility for community—including health, no fear of death, and for those who are wealthy and powerful to use these advantages not to exploit those less fortunate but rather to help them. (Karenga, 2003). In ancient Hindu philosophy, the transcendent character of human life is expressed through principles of the sanctity and quality of life. Further, individuals – and society – have the duty to preserve and guard individual and communal health and to rectify imbalances in the processes of nature, and to correct and repair states that threaten life and well-being, of both human and non-human species. The Judaic principle of tikun olam is the imperative to repair the world, reflecting the divine values of justice (tzedek), compassion (hesed) and peace (shalom). According to Kern (2006), “the traditional practice of applying principles of Halacha to ethical dilemmas and the evaluation of new technologies defines Jewish bioethics. This process attempts to identify the duties of physicians, patients and families faced with life, health and death decisions.” Kern describes three primary ethical principles grounded in Judaism: that human life has infinite value; that aging, illness and death are a natural part of life; and that improvement of the patient’s quality of life is a constant commitment. The Hippocratic principles – broader and more complex than the well-known Hippocratic Oath – address a broad range of practical concerns, including establishing trust with the patient as a means of a “proper prognostic.” (Bartz, 2002) Christian principles of charity, the sanctity of human life, and the assumption of an afterlife, while differently interpreted by the varying denominations of Christianity, have served as a platform for

much of the Western discourse and principles regarding bioethics. In Islam, one Hadith (oral tradition which forms a basis for Islamic jurisprudence) made treatment mandatory when available, and if withholding treatment would be harmful. Another stipulated that physicians/healers should be discouraged from using any treatment if the benefit is not certain or harm is feared. The Iranian Islamic scholar and religious leader Abu Bakr Mohammad Ibn Zakariyya al-Razi created the first set of basic standards for medical ethics. (National Library of Medicine, 1998). In much of recent Western discourse regarding bioethics – through published books and articles, conferences, and national or international fora to derive guidelines and principles, for example with respect to genomics— the “history” bioethics is traced from either immediately post-Nuremburg or to the early 1970s, with the creation within one year of the Institute of Society, Ethics and the Life Sciences – now the Hastings Center – and the Kennedy Institute of Ethics at Georgetown University, in 1970 and 1971, respectively. To do so not only discounts the extraordinary wealth and diversity of thought in this complex area, but also limits the opportunities for careful consideration of the bioethical issues which abound in the rapidly evolving health sciences. In late 2005, the Universal Declaration on Bioethics and Human Rights was adopted – by acclamation – by General Conference of the United Nations Education, Scientific and Cultural Organization (UNESCO). This document “anchors the principles it endorses in the rules that govern respect for human dignity, human rights and fundamental freedoms.” (UNESCO, 2006) The Declaration called for members to respect 15 principles. They reflect not only the diversity of UNESCO members but also harkens back to principles as old as Pharonic Egypt and as new as the American founders of the bioethics academy. The principles are: human dignity and human rights, benefit and harm, autonomy and individual responsibility, consent, special protection for persons without the capacity to consent, respect for human vulnerability and personal integrity, privacy and confidentiality, equality, justice and equity, non-discrimination and non-stigmatization, respect for cultural diversity and pluralism, solidarity and cooperation, social responsibility and health (which includes access to care, among other rights), sharing of benefits, protecting future generations, and protection of the environment, the biosphere and biodiversity. (UNESCO, 2006) These principles are very specifically to be applied not only to the conduct of research but to decisionmaking at the clinical and broad policy levels, including for example the as-

Bioethics and Public Diplomacy: Dialogue through Shared Concerns, Vital Questions Irene Anne Jillson, PhD Bioethics as practically considered and applied to individual clinical practice and public health – not the academic field, which is usually traced to 1970— has been a concern across cultures, spiritual beliefs and nations for millennia. There are notable consistencies among the diverse principles that derive from this concern.

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sessment of risk related to medicine, life sciences and associated technologies. They also apply to transnational policies regarding research, bioterrorism, and illicit traffic in organs, genetic resources and so forth. As part of its mission to address ensure that this Declaration is respected by member countries, UNESCO has an extensive program of providing assistance to developing countries in setting up bioethics committees (that address bioethics generally), an ethics education program, a data base of ethics institutions, legislation and guidelines, and other information. (UNESCO 2009) The World Health Organization (WHO) also addresses ethical issues of human genomics. Of particular concern to WHO is that, as the field of pharmacogenomics continues to expand, “there is a similar growth in the understanding and ability to appropriately address the ethical, legal and social implications” that its research and development raises. There is, WHO notes, “a lack of evidence on its impact in the context of developing countries” calling for consideration of “the extent to which pharmacogenomics might contribute to the further marginalization of individuals whose conditions – and genetic peculiarities – put them in the minority of patient populations.” From pandemics – including HIV/AIDS, avian and H1V1 flu for example – to pharmacogennomics, from organ transplants to neonatal intensive care technology, and from access to basic health care to addressing high risk behaviors such as tobacco and opiate addiction, nation state and their populations daily face ethical conundrums that require thoughtful, transparent and clear discourse. This is not only a necessity – it is an opportunity for dialogue. The National Institutes of Health (NIH) Human Genome Project, UNESCO and other entities have promoted such dialogue. There are also increasing examples of individuals who are engaged in dialogue regarding bioethical issues who are from countries that at political odds with one another. Bioethicists at Jesuit colleges in England are engaged with counterparts in Islamic colleges in Qom, Iran. This is understandable: we face comparable health problems at the clinical, institutional, and national and international policy levels, and have both common bases for addressing them (e.g., the UNESCO principles) and differences with respect to philosophical and spiritual approaches. But discourse regarding these differences is both healthy and instructive. The abstracts from The Second International Congress of Medical Ethics in Iran (Tehran University, 2008) tell the story: there are more similarities in the discussion of complex bioethical issues than dissimilarities. The shared values with respect to sanctity of human life, responsibility for protection of vulnerable populations, and the imperative to

do no harm are a common thread throughout. This, then, is a call for expanded dialogue across nations and cultures, across religious beliefs and tribal boundaries, with respect to bioethics. Not only that. Perhaps bioethics can be a foundation for public diplomacy with both those nations with which cordial relationships are enjoyed, and those with which improved relationships are imperative for human rights, and humanity itself, to be protected and preserved.

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Works Cited Bartz, R. (2002) Remembering the Hippocratics: Knowledge, Practice and Ethos of Ancient Greek Physician-Healers. In: Kuczewski, MG and Polansky, R. Ancient Themes in Contemporary Issues. Cambridge, MA: MIT Press. Karenga, M. (2003) MAAT: The Moral Ideal in Ancient Egypt. Ropuledge. Kern, P. (2006) Bioethics in Judaism Accessed on April 20 at: <http://ijs.org.au/Bioethical-issues-in-Judaism/default.aspx>. Martensen, R (2001) The History of Bioethics: An Essay Review. Oxford University Press, Vol. 56, pp. 168-175. National Library of Medicine (1998). Islamic culture and the medical arts. Bethesda, MD: National Library of Medicine. UNESCO (2005) Universal Declaration on Bioethics and Human Rights. New York: United Nations Educational, Scientific and Cultural Organization. UNESCO (2009) Global Ethics Observatory (GEObs). Access on April 22 at: <http://portal.unesco.org/shs/en/ev.php-URL_ ID=6200&URL_DO=DO_TOPIC&URL_SECTION=201. html>. Van den Dungen, W. (2003). World Health Organization (2009) Ethical, Legal and Social Implications (ELSI) of human genomics. Accessed on April 20 at: <http://who.int/genomics/elsi/pharmacogenomics/en/>.