The Ethics of PGD - Part 1

Transcription

1 DEVELOPMENT OF PGD/HLA DEBATE Part One Published Statements and Opinions Research methodology: The methodology for this review was subjective but informed. The websites of relevant professional and international bodies were studied for recent views on the debate. A control search was performed using the Google search engine (keywords: committee view PGD HLA. This returned one additional document which was not a committee opinion but the summary of a recent conference on prenatal testing in the Netherlands. This document is supplied in the annex to this report. This report is divided into 3 parts. Part 1 reports on the national opinions, part 2 surveys the international opinions and part 3 focuses on published opinions by European ethics councils. The evidence level corresponds to 1Vb (authoritative statements from expert review and/or opinions).

2 I. NATIONAL OPINIONS 1. BMA The BMA's Annual Representative Meeting in July 2003 welcomed the Court of Appeal s judgment allowing parents to use PGD to select an embryo on the basis of their genetic information in order to allow treatment of a seriously ill family member. 1 The judgment also reflects the view of the BMA s Medical Ethics Committee. The MEC recommended that the BMA should "support, in principle, the use of PGD combined with tissue typing in all cases where this was the only possibility of treatment for a sibling whose condition was lifethreatening or sufficiently serious to justify the use of PGD". This view was adopted as BMA policy. Furthermore, the MEC recommended that selection of an embryo should also be allowed in cases where there is no risk of a serious genetic disorder, but where selection is requested solely to allow treatment of a seriously ill sibling. 2 They argue that any objection to using HLA typing in the absence of genetic condition (Whittaker case), on grounds that it does not benefit the embryo, is questionable since PGD to avoid a serious disorder also does not benefit the affected embryo which would be destroyed. Even if there was a perceived risk for the created child as a result of being exposed to the PGD procedure this would necessarily mean that it should be prohibited. This is because parents expose their children to other risks for the benefit of other people, such as participation in research, provided those risks are minimal. Any risk of harm would also need to be balanced against the psychological benefits to the donor, and the family unit as a whole, from saving the life of a dying child. It would therefore be acceptable to extend the use of embryos (in addition to improving fertility treatment etc.) and permit their use to save a child s life. The Committee concludes that there is no morally relevant difference between the two cases; this view was accepted by the Board of Professional Activities. The BMA recognizes the importance of the welfare of the child born as a result of the treatment but feels that recognition of this welfare is not incompatible with selection on the basis of tissue type alone. It recommends certain safeguards including the counselling of parents in advance. The same safeguards as in other sibling to sibling transplants should apply in case the cord blood transplant should fail. In a briefing paper to Parliament in October 2003 the BMA expressed the hope that the necessary legislative changes will be made to allow selection by tissue typing where this is the only possible treatment for the sibling. This would allow those needing this treatment to benefit from the safeguards and regulatory mechanism in the UK, rather than having to seek the treatment overseas. 2. HGC (formerly ACGT) No opinion published since In its response to the HFEA on the outcome of the joint HFEA/ACGT consultation on PGD the HGC recommend that PGD should be limited to specific and serious conditions. 3 The issue of PGD/HLA typing was briefly raised at the first meeting of the HFEA/HGC joint working party on PGD in December 2000 where the difficulties of this issue were acknowledged but no further information is available. At the meeting of the Genetic Testing Sub-Group in February 2001 several members expressed concern that PGD should not be used for positive selection Nuffield Council on Bioethics 1 BMA Ethicsbrief Issue 66, September 2003, available at URL=< 2 Ethicsbrief of the Annual Representatives Meeting, 3 Paper HGC01/P2, Preimplantation Genetic Diagnosis, 4

3 No published opinion on PGD/HLA. 4. Royal College of Obstetricians and Gynaecologists Discussion document in preparation. 5. British Fertility Society In its response to ACGT/HFEA consultation in 2000 the BFS argues that care must be taken if a government authority is in charge of regulation. Such regulation effectively legitimises a role for the state to allow or prohibit the birth of an individual based on identification of its genetic composition. This might legitimise discrimination against disabled individuals. The BFS recommends that HFEA should not be given power to make decisions about the tests that can be offered for PGD. The final decision should rest with the parents. 5 II. INTERNATIONAL OPINIONS 1. ESHRE ESHRE Ethics Taskforce on PGD (2003) 6 Recommend multidisciplinary approach. They refer to two ethical principles (1) the welfare of the child and (2) reproductive autonomy. They consider the benefits for the receiving sibling to outweigh the disadvantages for the future child. Also consider PGD/HLA as morally acceptable if child is not used solely as means to an end. They express no explicit view on HLA testing without simultaneous screening for inherited disorder but their arguments would seem to be applicable to both PGD/HLA and HLA only. At the forthcoming ESHRE conference in Berlin the Special Interests Groups for Reproductive Genetics and for Law and Ethics will be organising a pre-congress course on the ethical and political issues concerning PGD/HLA (among other topics). 2. UNESCO International Bioethics Committee (IBC) The IBC s report on Pre-implantation Genetic Diagnosis and Germ-line Intervention 7 does not make any general statement about the moral status of human prenatal life but adopts a pluralistic approach. They consider PGD/HLA for purposes of screening for a specific blood disorder in the child to be born as ethically acceptable. But PGD with the only goal of HLA typing and selecting embryos as donors is ethically unacceptable. Moreover, PGD should be restricted to medical indications. The Committee recommends more psychosocial studies to evaluate influence of availability of PGD on social pressures, parent-child interactions and impact on disabled people. Intergovernmental Bioethics Committee (IGBC) Endorses above findings WMA No explicit opinion on PGD/HLA. But the WMA Declaration of Ottawa on the Rights of the Child to health care (October 1998) 9 might be relevant. The general principles of this The ESHRE Ethics Task Force, Taskforce 5: preimplantation genetic diagnosis (2003) Human Reproduction 18 (3) , April 2003, 8 Recommendations of the Third Session of the IGBC (23/24 June 2003), n.pdf 9

4 declaration state that every effort should be made to protect to the maximum extent possible the survival and development of the child. 4. United States President s Council on Bioethics (successor to National Bioethics Advisory Commission) In its recent report 10 the Council discusses PGD and embryo selection generally. The Council notes that whereas it is not known whether embryo biopsy affects the development of the child later born studies on this are currently underway in Europe. It regards positive selection for designer babies as currently not on the horizon. It cites means to an end argument as a possible risk especially if PGD should be used for non-medical or enhancement purposes. It also suggests that PGD risks normalizing the idea that a child s genetic make-up is quite properly the concern of parental reproductive choice. New technologies may change parental attitudes and expectations towards their children. It considers the wider societal effects of limiting reproductive choice due to social pressures. But notes that these concerns may be unjustified and premature. PGD could be seen as one way of expressing parental responsibility for the care of one s offspring It briefly discusses PGD/HLA specifically. This poses the additional ethical concern of deliberately creating and selecting a child to benefit another. The Council questions whether it is proper to assign to a child a saviour role and give it life on condition that the child fulfil this role. 5. Australia Australian Health Ethics Committee (principal committee of the National Health and Medical Research Council) The NHMRC have proposed a draft on Ethical guidelines on the use of reproductive technology in clinical practice and research which closed for public consultation in March The guidelines propose that PGD should only be used to obtain information about a serious genetic condition or disease. 11 Once issued these guidelines will replace previous NHMRC guidelines on reproductive technology and will form part of the new legislative framework to regulate reproductive technologies under the Research Involving Human Embryos Act Infertility Treatment Authority, Victoria, Australia The ITA s policy 12 allows PGD/HLA to select embryos that do not have a genetic disease and are HLA compatible. This is in accordance with the first two guiding principles of the Infertility Treatment Act 1995 which state that the welfare of the child to be born is paramount and that human life should be preserved and protected. The ITA further draws attention to three further ethical considerations when reviewing an application. These are (1) the motivation and level of understanding of the parents (which it considers difficult to identify), (2) the issues that may arise when the sick sibling is not cured and (3) the status and relationships of the child within the family. III. EUROPEAN UNION 1. Council of Europe Report by the working party on the Protection of the Human Embryo and Foetus (June 2003) 10 Reproduction and Responsibility: The Regulation of New Biotechnologies, March 2004, 11 National Health & Medical Research Council, Ethical guidelines on the use of reproductive technology in clinical practice and research (Draft, February 2003), section 8.1, document available at URL=< 12 Infertility Treatment Authority, Tissue typing with preimplantation genetic diagnosis (reviewed January 2003), document available at URL=<

5 Rather than represent an opinion the report acknowledges and reflects diverse opinions of the working party and is intended to advance ethical discussion. One of the arguments against the use of PGD/HLA is that it would distort the original purpose of PGD since the child will not be conceived for his/her own sake but for the benefit of another. In this context, some emphasize the importance of establishing the parents motivation for having a child but recognize that in practice this would be difficult. They envisage difficulties in situations where embryo was free of disease but HLA incompatible. In circumstances where the embryo is unaffected but not HLA compatible the question of the moral status of the embryo is raised. If a healthy but incompatible embryo were destroyed this would constitute instrumentalisation of the embryo. On the other hand parents might genuinely wish to have another, healthy child. Even though PGD for purposes of HLA typing alone offers no benefits to the embryo the procedure is nevertheless for the benefit of family solidarity. Furthermore for the benefit of social solidarity society should allow parents to have access to potentially life saving treatment. The Council recommends non-directive counselling to ensure that the welfare of the future child is carefully considered. Parents also need to consider in advance the potential failure of an umbilical cord blood transplant. 2. Denmark Danish Council of Ethics In their resumé of recommendations 13 on Microinsemination and pre-implantation genetic diagnosis (PGD) (2003) all sixteen members of the council consider it ethically unacceptable for PGD to be used to obtain compatible tissue type. No reasons given. 3. Sweden In January 2004 the Swedish National Council on Medical Ethics published an opinion on PGD. This document is currently being translated. 4. France National Ethics Committee for Life Sciences and Health 14 (July 2002) In this report 15 the Committee considers the specific case of an application to apply PGD/HLA to treat a child with Fanconi s Anaemia. In their summing up the Committee conclude that to choose a child solely on the basis of HLA compatibility is unacceptable. Ethical reasoning on PGD/HLA The Committee identifies the authenticity of the parental project as the essential problem and the potential risk of the child becoming a commodity. Specifically, the legitimate wish to bear a child does not equate the right to a child object. But these concerns do not rule out possible secondary benefits to others as long as the child s welfare remains paramount. On the issue of selection, the Committee point to a distinction between a negative choice in PGD and the positive choice that is made when selecting an HLA compatible embryo. They do not see the selection between different unaffected and HLA compatible embryos as problematic since choice is inherent to IVF where the number of transferred embryos is always kept to a minimum. However, if only unaffected but incompatible embryos are produced and subsequently rejected for implantation this may indicate the true parental motivation and would risk the embryo being instrumentalised. But since selection is inherent to IVF why should it not be possible to make a positive choice regarding a particular characteristic? Specifically, why should leaving the choice to fate represent a higher moral ground than making a deliberate choice on grounds of a particular characteristic. Especially if, in the case of HLA, the selection is socially neutral, the outcome of producing a healthy and compatible embryo can be viewed as good (2003) 14 Comité Consultatif National d Ethique pour les sciences de la vie et de la santé, URL=< 15 Reflections concerning an extension of preimplantation genetic diagnosis

6 With reference to Kant s dictum (never solely as a means, but always as an end) is instrumentalisation unavoidable? Immune compatibility could be seen as a form of solidarity born of brotherhood. The child will still be a singular being with unique life projects. But in the medium to longer term the question of a possible compulsion to donate in case of treatment failure cannot be ignored. The Committee cite Paul Ricoeur who sees PGD/HLA as a confrontation between the situation of a child about to die, and that of a child who may be entering a lifetime of constraint. What will happen in practice? Ideally, healthcare professionals will transfer unaffected, compatible embryos if available. A woman should not be forced to accept an incompatible embryo she rejects. But potential problems and moral conflicts that such a scenario would bring to both the woman and the healthcare professional must be anticipated. Safeguards 1. Possible psychological risks to the child must be considered. Here a comparison with traditional transplantation may give an insight into psychological effects. 2. Parents must be made aware of the possibility of failure and consider how they would adapt to such a situation. Moreover future pressure on the compatible child to donate bone marrow and parents should be alerted to these potential pressures. Future concerns PGD/HLA might be extended for use of cousins, other family members and parents. Any improved future application of the techniques may lead to systematically HLA compatible families able to mutually and endlessly repair each other. Principle of lesser evil is understandable but balance between reasonable therapeutic effort and excessive obstinacy must be struck. In conclusion the committee formulate two requirements: 1. Wish to undergo the procedure must represent a true parental project. 2. Searching for immune compatibility must take second place. 5. The Netherlands The Science and Ethics Advisory Committee of the Royal Netherlands Academy of Arts and Sciences published a report of a symposium entitled Prenatal testing new developments and ethical dilemmas. This was a collection of lectures and discussions by Dutch geneticists with some European contributions. 16 Some of the participants are members of the UNESCO International Bioethics Committee. 16 Royal Netherlands Academy of Arts and Sciences, Prenatal testing new developments and ethical dilemmas, symposium of 18 June 2003, report published 2004 available at

7 Part 2 Literature review of ethical arguments relevant to saviour siblings Research methodology: The HFEA does not have access to specialized search engines such as Social Sciences Citation Index or Philosopher s Index. The search strategy for this review of abstracts therefore consisted of a search of PubMed, a service provided by the National Library of Medicine which also covers MEDLINE. 17 In addition, a complete search of a selection of leading peer-reviewed journal publications (no anthologies or monographs) in academic bioethics was conducted going back to the year One book review was included. The PubMed results were edited to primarily include articles published since 2000 with particular relevance to the PGD/HLA debate. This also included articles relevant to the ethics of bone marrow and organ donations from children. Earlier articles on the ethics of PGD in general (for example, discussions focussing mainly or solely on the moral status of the embryo) were excluded. The journals searched were: Journal of Medical Ethics Cambridge Quarterly of Healthcare Ethics Bioethics Theoretical Medicine and Bioethics Hastings Center Report (no abstracts available) The following biomedical journals were included in the search: Human Reproduction Human Reproduction Update BMJ (searched for keywords PGD HLA) The review is divided into 4 parts. Part 1 and part 2 comprise selected abstracts of a PubMed search on PGD and bone marrow transplantation. Part 3 provides selected abstracts of the academic literature. Part 4 includes relevant titles from the Hastings Center Report. We were also sent a copy of Professor Guido Penning s recent paper on PGD/HLA. The paper and a summary of its main arguments are attached. The evidence level of the literature presented corresponds to 1Vb (authoritative statements from expert reviews an/or opinions). 17 A recent study showed that in order to obtain adequate coverage of (especially European) bioethical literature several database searches have to be combined. Among the single database searches MEDLINE was shown to have the second highest coverage (22.1%). Fangerau, H., Finding European bioethical literature: an evaluation of the leading abstracting and indexing services, Journal of Medical Ethics (2004)

8 Part 2.1 PubMed Search terms entered: PGD ethics 1: Med Law. 2003;22(3): Ethical considerations of applications of preimplantation genetic diagnosis in the United States. Adams KE. Oregon Health and Sciences University, Department of Obstetrics and Gynecology, Portland, Oregon, USA. Preimplantation genetic diagnosis (PGD) was developed to offer diagnosis of genetic disorders prior to initiation of a pregnancy, whereas previously such disorders would be diagnosed at amniocentesis or chorionic villus sampling after a pregnancy had already been undertaken. Such application of this technology is not controversial. But PGD has been used to not only diagnose genetic disorders but also to select for certain other characteristics, and this use of the technique is much more controversial. A case is presented in which PGD was used not only to select against a genetic disorder, but to select for a certain HLA type which matched an affected sibling. The new child's cord blood was transplanted into his affected sister, who subsequently was found to be free of disease. The ethics of "having a child to save a child" are explored, and possible other uses of PGD that lead to eugenic outcomes are considered. The lack of regulation of this technology in the US is contrasted with existing legislation in other countries, and the need for national and international consensus regarding appropriate uses of PGD is emphasized. Legal Cases 2: J Med Ethics Aug;29(4): Comment in: J Med Ethics Aug;29(4): Extending preimplantation genetic diagnosis: medical and non-medical uses. Robertson JA. Law School, University of Texas, 727 Dean Keeton Street, Austin, Texas, USA. jrobertson@mail.law.utexas.edu New uses of preimplantation genetic diagnosis (PGD) to screen embryos prior to transfer raise ethical, legal, and policy issues that deserve close attention. Extensions for medical purposes, such as to identify susceptibility genes, late onset disease, and human leukocyte antigen (HLA) matching, are usually ethically acceptable. Whether embryo screening for gender, perfect pitch, or other non-medical characteristics are also acceptable depends upon the parental needs served and the harm posed to embryos, children, and society. Speculations about potential future uses of PGD should not prevent otherwise acceptable current uses of PGD.

9 2: Hum Reprod Update Jul-Aug;9(4): Evolving ethics in medically assisted reproduction. Pennings G, de Wert G. Free University Brussels, Department of Philosophy, Pleinlaan 2, 1050 Brussels, Belgium. Ethical problems arising from the application of assisted reproductive technology are discussed for four specific areas, namely embryo research, multiple pregnancies, preimplantation genetic diagnosis (PGD) for social sexing, and finally PGD with HLA typing. Review 3: Hum Fertil (Camb) Feb;6(1):23-5. Use of preimplantation genetic diagnosis to produce tissue donors: an irreconcilable dichotomy? Gavaghan C. School of Law, University of Glasgow, Glasgow G12 8QQ, Scotland, UK. In 2002, the Human Fertilisation and Embryology Authority (HFEA) published its decision in the case of Raj and Shahana Hashmi. The couple had sought to use preimplantation genetic diagnosis (PGD) to have a child that could be a viable donor for their son, Zain, who has thalassaemia. The HFEA decided that PGD could, in the present case, go ahead. Later in 2002, the HFEA reached the opposite decision in the superficially similar case of Michelle and Jayson Whitaker. This paper will present a critical overview of the decisions of the HFEA in these two cases, and of the opinions and discussions the HFEA published in support thereof. Although it is acknowledged that the two cases differ to some extent in their facts, it is argued that the difference upon which the HFEA relied is one without ethical significance. Case Reports Review 4: Hum Reprod Mar;18(3): Comment in: Hum Reprod Jul;18(7): Extending preimplantation genetic diagnosis: the ethical debate. Ethical issues in new uses of preimplantation genetic diagnosis. Robertson JA. School of Law, The University of Texas, 727 Dean Keeton Street, Austin, Texas, USA. jrobertson@mail.law.utexas.edu The use of preimplantation genetic diagnosis (PGD) to screen embryos for aneuploidy and genetic disease is growing. New uses of PGD have been reported in

10 the past year for screening embryos for susceptibility to cancer, for late-onset diseases, for HLA-matching for existing children, and for gender. These extensions have raised questions about their ethical acceptability and the adequacy of regulatory structures to review new uses. This article describes current and likely future uses of PGD, and then analyses the ethical issues posed by new uses of PGD to screen embryos for susceptibility and late-onset conditions, for HLA-matching for tissue donation to an existing child, and for gender selection. It also addresses ethical issues that would arise in more speculative scenarios of selecting embryos for hearing ability or sexual orientation. The article concludes that except for sex selection of the first child, most current extensions of PGD are ethically acceptable, and provides a framework for evaluating future extensions for nonmedical purposes that are still speculative. Review 5: Prenat Diagn Dec;22(12): Issues and concerns of couples presenting for preimplantation genetic diagnosis (PGD). Katz MG, Fitzgerald L, Bankier A, Savulescu J, Cram DS. Monash Institute of Reproduction and Development, Monash University, Clayton, VIC 3168, Australia. mandy.katz@med.monash.edu.au BACKGROUND: The use of preimplantation genetic diagnosis (PGD) to select genetically 'normal' human embryos and to transfer them to the uterus of a woman has generated considerable controversy. Debate has occurred over the implications of PGD, sex selection, safety of embryonic manipulation and eugenics. This study evaluates a range of social and moral concerns of couples towards PGD and assisted reproductive technologies (ART) prior to treatment to obtain unbiased authentic attitudes independent of the treatment cycle and the outcome. METHODS: A total of 121 subjects were administered a structured questionnaire after each couple's in vitro fertilization (IVF) or genetic counselling session. Group A consisted of 41 subjects presenting for PGD of single gene disorders (PGD-SG) and group B consisted of 48 subjects undertaking PGD for aneuploidy screening (PGD-AS). A control group consisted of 32 subjects that were about to commence their first IVF cycle. RESULTS AND DISCUSSION: All groups found PGD to be a highly acceptable treatment. They expressed little concern about its extension to testing non-disease states such as sex and they were strongly in favour of a shared decision-making model in which couples have considerable autonomy over decisions about the embryo(s) to transfer. Differences between the groups included issues surrounding the transfer of embryos, restrictions to PGD and the destruction of embryos. 6: Bioethics Oct;15(5-6): Procreative beneficence: why we should select the best children. Savulescu J. Ethics Program, The Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Rd, Parkville, Melbourne, Victoria 3052, Australia. savulesj@cryptic.rch.unimelb.edu.au Eugenic selection of embryos is now possible by employing in vitro fertilization

11 (IVF) and preimplantation genetic diagnosis (PGD). While PGD is currently being employed for the purposes of detecting chromosomal abnormalities or inherited genetic abnormalities, it could in principle be used to test any genetic trait such as hair colour or eye colour. Genetic research is rapidly progressing into the genetic basis of complex traits like intelligence and a gene has been identified for criminal behaviour in one family. Once the decision to have IVF is made, PGD has few 'costs' to couples, and people would be more inclined to use it to select less serious medical traits, such as a lower risk of developing Alzheimer Disease, or even for non-medical traits. PGD has already been used to select embryos of a desired gender in the absence of any history of sex-linked genetic disease. I will argue that: (1) some non-disease genes affect the likelihood of us leading the best life; (2) we have a reason to use information which is available about such genes in our reproductive decision-making; (3) couples should select embryos or fetuses which are most likely to have the best life, based on available genetic information, including information about non-disease genes. I will also argue that we should allow selection for non-disease genes even if this maintains or increases social inequality. I will focus on genes for intelligence and sex selection. I will defend a principle which I call Procreative Beneficence: couples (or single reproducers) should select the child, of the possible children they could have, who is expected to have the best life, or at least as good a life as the others, based on the relevant, available information. 7: Haemophilia May;8(3): Ethical issues in the genetic aspects of haemophilia. Shenfield F. Reproductive Medicine Unit, EGA/UCH, London, UK. mfi@easynet.co.uk The aim of this paper is to put some of the ethical considerations concerning the genetic aspects of haemophilia not only in the national, but also in the international context, especially from the point of view of human rights. Particular attention is given to the issues pertaining to consent from children, and the respect for their autonomy within family relationships. This will be analysed within the context of genetic screening and testing, as well as codes of practice and guidelines. The specific issues around prenatal diagnosis in general and pre-implantation genetic diagnosis (PGD) are also discussed. Review 8: Hastings Cent Rep Mar-Apr;32(2):6. Sex selection: final word from the ASRM Ethics Committee on the use of PGD. Robertson J. Publication Types: News 9: Hum Reprod Mar;17(3): Ethical considerations on preimplantation genetic diagnosis for HLA typing to match a future child as a donor of haematopoietic stem cells to a sibling. Pennings G, Schots R, Liebaers I.

12 Department of Philosophy, Lok. 5 C 442, Academic Hospital, Free University Brussels, Pleinlaan 2, B-1050 Brussels, Belgium. gpenning@vub.ac.be Recently, several requests were made by couples with an affected child who wanted preimplantation genetic diagnosis (PGD) to select embryos in the hope of conceiving an HLA identical donor sibling. This article considers the ethical arguments for and against the application of PGD for this goal. Only embryos HLA matched with an existing sibling in need of a compatible donor of haematopoietic stem cells would be transferred. The main arguments are the instrumentalization of the child, the best-interests standard, the postnatal test for acceptability and the experience of the donor child. It is argued that conceiving a child to save a child is a morally defensible decision on the condition that the operation that will be performed on the future child is acceptable to perform on an existing child. The instrumentalization of the donor child does not demonstrate disrespect for its autonomy or its intrinsic worth. Review

13 Part 2.2 PubMed Search terms entered: bone marrow transplant ethics 1: Monash Bioeth Rev Oct;22(4): Tissue typing for bone marrow transplantation: an ethical examination of some arguments concerning harm to the child. Grundell E. Faculty of Law, University of Melbourne, Australia. Tissue typing (TT) is a recent and controversial scientific advance. Whilst its current applications can easily be described as pro-therapeutic and within the realms of preventative medicine, its specificity and potential are often characterized as the tip of the eugenic iceberg: undermining the very basis of individual autonomy and identity in an inevitable march towards the perfect society. In addition to arguments concerning societal harms flowing from TT, significant concerns have also been raised concerning harms to the future child born as a result. In the context of current legislation and policy, this article examines two aspects of arguments concerning harm to the future child: those relating to psychological harms, and those arguing that TT is contrary to the future child's best interests. The article examines the moral basis for arguments concerning harm to the future child. It proposes that arguments concerning psychological harm may overlook or minimise the potential benefits flowing from the broader social, familial context into which the child is born. These arguments may be countered, or at least balanced, by considering the future child in this context. In relation to arguments that TT is contrary to the future child's best interests, the paper examines a non-standard consideration of best interests. It argues that this standard should be used in considering whether or not TT for bone marrow transplant is harmful to the future child, thereby extending moral consideration of interests to intra-familial interests and outcomes. On this basis, it can be argued that TT is not contrary to the interests of the future child. The paper concludes by noting a potential tension between the first guiding principle of the Infertility Treatment Act 1995 (Vic) and the current Victorian policy on TT. 2: Bone Marrow Transplant Jun;19(12): Transplant of bone marrow and cord blood hematopoietic stem cells in pediatric practice, revisited according to the fundamental principles of bioethics. Burgio GR, Locatelli F. Department of Pediatrics, University of Pavia, IRCCS Policlinico San Matteo, Italy. The two most widely used sources of hematopoietic stem cells for allogeneic transplants in pediatric practice are bone marrow (BM) and cord blood (CB). While bone marrow transplantation (BMT) is reaching its 30th year of application, human umbilical cord blood transplantation (HUCBT) is approaching its 10th. Although these procedures have basically the same purpose, a number of biological differences distinguish them. In particular, the intrinsically limited quantity of CB stem cells and their immunological naivete confer peculiar characteristics to these hematopoietic progenitors. From a bioethical point of view, the problems which have repeatedly been raised when the BM donor

14 is a child are well-known. Different but no less important ethical problems are raised when one considers HUCBT; in this regard the most important issues are the easier propensity of programming a CB donor in comparison with a BM donor (clearly due to the shorter time interval needed to collect the hematopoietic progenitors); the in utero HLA-typing; the implication of employing 'blood belonging to a neonate' for a third party; the need to perform a number of investigations both on the CB of the donor and on the mother and the implications that the discovery of disease may have for them, but also the need to establish banks for storing CB, with the accompanying administration and management problems. All these different aspects of UCBT will be discussed in the light of the four fundamental and traditional principles of bioethics, namely autonomy, nonmaleficence, beneficence and justice. Review 3: Br Med Bull. 1997;53(4): The ethics of organ donation. Dunstan GR. Department of Theology, University of Exeter, UK. As organ transplantation is physically possible within a tension between common biological properties and individual immunities, so it is ethically possible within a tension between individual personality in full integrity and the human community of which each member, social by nature, is an organic part. Ethical donation is by consent, explicit or presumed, spontaneously offered or procured by request. Altruism or commercial dealing is now a live issue in organ procurement, whether cadaveric or by live donation, related or unrelated. Attention is given to children in transplantation, and to new developments with fetal organs, neural tissue, bone marrow and xenografts. Given all that medical science and skill can now offer, patients are still free to decline. Review 4: Bone Marrow Transplant Nov;18 Suppl 2:8-12. Ethical problems in bone marrow transplantation in children. Massimo L. Department of Pediatric Hematology and Oncology-G.Gaslini Children's Research Hospital, Genova-Italy. The medical staff caring for children with hematological or oncological diseases is often faced with delicate ethical and, at times, legal problems. Although many of these are common to other branches of pediatrics where patients are children lacking decision-making capacity, others, such as bone marrow transplantation (BMT), are peculiar to this specialty. This is a vanguard treatment for a wide range of diseases that are either incurable or resistant to conventional therapies. If the patient does not have a related donor, ethical and legal problems can occur: profound emotional dilemmas arise both because of the fretful search for a donor and because of the limited period the patient can be transplanted with good expectations of success. National and International Registries are linked to all BMT Units for the identification of compatible donors with the recipient. Hospitals hosting a BMT Unit must fulfill several requirements which are crucial to guaranteeing the best results when faced with

15 the complexity and aggressiveness of transplantation and possible complications, such as a blood bank, an infectious diseases department, a rehabilitation unit, the availability of consultants, as well as playworkers, teachers, psychologists and social workers. Any trial carried out in a Center without sufficient experience, simply pleading the concept of "last hope" is not ethical, even considering possible late effects and sequelae. For allogeneic bone marrow transplantation it is necessary to obtain both the Consent of the donor and the Consent of parents of the recipient. Often the donor is a child sibling of the patient, lacking decision-making capacity as well. Information to parents of both children must be detailed. In reality, there are practically no risks for the child donor and, if any, they are linked to the general anaesthesia. The text of the Informed Consent is usually deliberated and accepted in advance by the Ethics Committee of the Institution where the patient is followed. Voluntary donor's Consent is required at different steps: at the entry in the Registry, when typing of major histocompatibility complex, at bone marrow harvesting under general anaesthesia. In Italy, Article No. 3, Law No. 107 of May 4, 1990 allows parents or legal guardians to consent to the bone marrow donation of a minor. Review 5: BMJ Jul 6;313(7048):50. Volunteering children for bone marrow donation. Children may be able to make their own decisions. Alderson P, Montgomery J. Letter 6: BMJ Jul 6;313(7048): Volunteering children for bone marrow donation. Studies show large discrepancies between views of surrogate decision makers and patients. Kent G. Letter 7: Obstet Gynecol Surv Aug;50(8): Umbilical cord blood for use in transplantation. Varadi G, Elchalal U, Shushan A, Schenker JG, Nagler A. Department of Bone Marrow Transplantation, Hadassah University Hospital Jerusalem, Israel. Bone marrow transplantation has rapidly progressed over the last two decades offering cure and prolonged disease-free survival for patients suffering from certain hemato-oncological malignancies or metabolic disorders. However, bone marrow transplantation is limited by the paucity of major histocompatibility loci antigen (HLA)-matched donors, and the morbidity and mortality due to graft-versus-host disease. Recently it has been shown, that umbilical cord blood represents a unique source of transplantable hematopoietic progenitor cells. Currently, human umbilical cord blood from a newborn sibling has been used successfully for hematopoietic reconstitution of approximately 40 children with congenital or malignant diseases. Establishment of umbilical cord blood banks

16 might alleviate some of the problems associated with bone marrow transplantation. The developments in this field which have occurred during the last decade, as well as the importance of cooperation between the obstetric and transplantation staff, are discussed in this review. Certain ethical problems remain surrounding the issue of using human umbilical cord blood for allogeneic transplantation which must be addressed. Review 8: Bone Marrow Transplant May;15(5): Ethical issue of bone marrow transplantation for thalassemia. Giardini C. Editorial. No abstract available. 9: Semin Oncol Nurs Feb;10(1): Ethical issues in bone marrow transplantation. Downs S. Baptist Cancer Center, Nashville, TN Ethical issues in health care arise from the perspectives of individual rights and clinical research. The advances in technologies for the treatment of cancer that come from clinical research have created new ethical issues. Bone marrow transplantation is such a case where research has the potential to benefit, but our resources to provide this lifesaving option are scarce. Ethical issues that nurses face in BMT include informed consent, concerns about the rights of donors, and the allocation of resources. Review 10: Blood Rev Mar;7(1):4-9. Bone marrow transplant for sickle cell disease--the dilemma. Davies SC. Department of Haematology, Central Middlesex Hospital, London, UK. Sickle cell disease is the family of clinically significant haemoglobin disorders which have in common the inheritance of the sickle beta haemoglobin chain gene. The homozygous SS condition, also known as sickle cell anaemia, can present a varied clinical picture from asymptomatic through to frequent painful vaso-occlusive crises and even death as a result of complications of the disease. S beta zero thalassaemia and the rate haemoglobin SD disease present a similar picture to SS, while S beta plus thalassaemia and haemoglobin SC disease generally have milder clinical features than SS and present somewhat later in life. The present debate about bone marrow transplant (BMT) for sickle cell disease, among both physicians and community, relates to SS patients, definition and markers of disease severity, the effect of BMT on sickle related organ damage, the efficacy of BMT for SS, and its complications, both early and long-term. Review

17 11: J Med Ethics Sep;18(3):125-7, 141. Baby marrow: ethicists and privacy. Zucker A. Ohio University. A family had a child in large part to use its marrow in the hopes of saving the life of an older child afflicted with leukaemia. Public response from medical ethicists was negative. This paper argues that what the family did was not clearly wrong and that the ethicists should not have made public pronouncements calling the morals of the family into question. Case Report 12: J Clin Epidemiol Jul;45(7): When philosophers shoot from the hip. Rachels J. Department of Philosophy, University of Alabama, Birmingham PIP: A visible result of the 20-year old applied ethics movement is the use of moral philosophers as quotable newspaper sources. In situations like the op-ed page, adequate space and time allows for serious reflection, and the columns provide accessible, quality ideas for the general public. Quality usually disappears when the newspaper interviews an ethicists for the next day's story. Reporters want a short, pithy quote, confirming their belief that alarming events really are alarming events. A conservative viewpoint usually results: new developments become troubling, not because of careful analysis, but because it challenges accepted wisdom. The New York times provided readers with immediate resistance to the idea that a family may decide to have a 2nd child in the hopes that that child will provide compatible bone marrow cells (a 1 in 4 chance) needed to save the life of the 1st-born child after a 2-year search for a suitable donor, with plans to love their baby. The Times quoted an ethicist saying: "It's outrageous that people would go to this length." But consider the question. Is it really better to let the older child die for some vague ethical fear? Parents choose to reproduce for many reasons unrelated to the unrealistic ideal of wanting to have a child solely for "that child's own welfare...each person [being] an end in...herself..." As commentators of public events, philosophers would do well to challenge the prevailing orthodoxy, questioning assumptions unthinkingly made. Instead they frequently serve as orthodoxy's most sophisticated defenders, assuming that the existing social consensus must be right and articulating its theoretical "justification." Or they rely on the "slippery slope" doctrine of fear, where departure form business-as-usual leads inextricably to frighteningly extreme consequences. The silliness of previous facile ethical pronouncements suggests the need for future caution.

18 13: Clin Res Dec;38(4): Bone marrow transplantation in sickle cell disease: the trade-off between early mortality and quality of life. Kodish E, Lantos J, Siegler M, Kohrman A, Johnson FL. Center for Clinical Medical Ethics (CCME), University of Chicago, Pritzker School of Medicine, IL : J Clin Ethics Summer;1(2):99-103; discussion Conceiving a child to save a child: reproductive and filial ethics. Jecker NS. Department of Medical History and Ethics, University of Washington School of Medicine. I conclude that Mary and Abe's decision to conceive a child to save a child does not impose harm on persons or on relationships in the family. Nor does it evince a lack of respect for the child they have conceived. The ethical guidelines that support this conclusion can now be summarized. First, actions should not depersonalize or otherwise endanger personal relationships. Second, although ideally personal relationships are initiated and continued for their own sake, after a personal relationship has been established and sustained the motives for establishing it recede in importance. Third, the requirement of honesty looms especially large in the context of personal relationships. Fourth, privacy protects personal relationships in the family from intrusion by the state. Fifth, even if those with whom we stand in personal relationships are not fully rational or self-conscious, we should treat them with respect. Finally, persons often are called upon to make greater sacrifices in personal relationships. These principles represent only the barest beginnings of an ethics for filial relationships. Nonetheless, they mark progress in the direction of developing a more complete account. We should not suppose that ethics in the family always will be spontaneous or "natural". Over a century ago, Mill warned that nature and natural are "one of the most copious sources of false taste, false philosophy, false morality, and even bad law". Especially in the wake of medical advances, such as recombinant DNA and new reproductive technologies, the complexity of filial ethics will only increase. The demographics of an aging society will add further complexity to filial contexts.(abstract TRUNCATED AT 250 WORDS)

19 Part 3 1. Spital, Aaron Donor Benefit is the key to justified living organ donation Cambridge Quarterly of Healthcare Ethics (2004), 13: Spurred by a severe shortage of cadaveric organs, there has been a marked growth in living organ donation over the past several years. This has stimulated renewed interest in the ethics of this practice. The major concern has always been the possibility that a physician may seriously harm one person while trying to improve the well-being of another. As Carl Elliott points out, this puts the donor's physician in a difficult predicament: when evaluating a person who volunteers to donate an organ, a doctor is in the position of deciding not simply whether a subject's choice is reasonable but whether he [the doctor] is morally justified in helping the subject accomplish it. 1 This question has become even more difficult since the introduction of living donor operations that are more risky than living kidney donation (e.g., adult-to-adult liver donation) and the suggestion that volunteers at added risk may sometimes be acceptable. 2 So, how can we decide when the risk is too much? 2. Sheldon, Mark Guest Editorial: Children as Organ Donors: A Persistent Ethical Issue Cambridge Quarterly of Healthcare Ethics (2004), 13: When I started doing clinical ethics rounds, in the mid 1980s, I decided to venture onto the pediatrics ward. The first patient I encountered was a 3-year-old girl returning to her room, groggy from general anesthesia. When I inquired about her, the nurse explained that she had just gone through the procedure to donate bone marrow for her 1-year-old sister, who was preparing to undergo bone marrow transplantation for leukemia. 3. Zinner, Susan Cognitive Development and Pediatric Consent to Organ Donation Cambridge Quarterly of Healthcare Ethics (2004), 13: Attempting to balance the needs and interests of minors with the obligation to protect them from their own potentially harmful decisions poses an ethical challenge for the physician. This problem is further exacerbated when the context is not medical treatment but organ donation. That is, medical treatment scenarios generally involve decisions likely to result in objective improvements to the minor's health status. Consent to organ donation, however, raises several vexing problems. First, how should the provider measure both the cognitive ability and competence to consent of the minor to ensure that the minor comprehends the risks and benefits of donation and that no coercion is involved? Second, given that improvement of one's health is an unlikely scenario, is there a way to measure subjective determinations of satisfaction and altruism enjoyed by a minor following organ donation? If so, should the physician regard these values in a manner analogous to physical improvement? Finally, are parents the appropriate decisionmakers for their children when a sibling-to-sibling donation occurs? Is it possible for parents to always act in the best interests of both children in this event?

20 4. Jansen, Lynn A. Child Organ Donation, Family Autonomy, and Intimate Attachments Cambridge Quarterly of Healthcare Ethics (2004), 13: What standard or principle should guide decisionmaking concerning the permissibility of allowing children to be organ donors? For a long time, it has been widely assumed that the best interest of the child is the appropriate standard. But recently, several critics have charged that this standard fails to give due weight to the interests of the family and the intimate relationships that the family makes possible. 1,2 This article reviews and rejects both the bestinterest standard (as it has been traditionally conceived) and the alternative standard recommended by the critics. I then propose a new standard to help parents, healthcare professionals, and judges decide when it is and is not permissible for children to serve as organ donors. This new standard modifies and broadens the best-interest standard to allow it to account adequately for the contribution that intimate relationships make to the well-being of children. 5. Ekman Ladd, Rosalind The Child as Living Donor: Parental Consent and Child Assent Cambridge Quarterly of Healthcare Ethics (2004), 13: Despite the much-discussed court cases in the 1970s that permitted some sibling-to-sibling kidney donations from minors, 1 principles that can guide parental, medical, or judicial decisionmaking are neither clearly articulated nor uncontroversial. 6. Pentz, Rebecca D., Chan, Ka Wah, Neumann, Joyce L., Champlin, Richard E., and Korbling, Martin Designing an Ethical Policy for Bone Marrow Donation by Minors and Others Lacking Capacity Cambridge Quarterly of Healthcare Ethics (2004), 13: The child was 2 years, 8 months old and weighed 25 pounds, one-fifth the weight of her mother, for whom she was to be the bone marrow donor. The mother had suffered a relapse of acute myelogenous leukemia; her physicians recommended a bone marrow transplant. The child was the closest human leukocyte antigen (HLA) match and thus the best donor candidate for her mother's transplant. 7. Holm, Søren The Child as Organ and Tissue Donor: Discussions in the Danish Council of Ethics Cambridge Quarterly of Healthcare Ethics (2004), 13: At the end of 1999 the Danish Council of Ethics published a report on organ and tissue donation from living donors. The report focused on kidney and bone marrow transplantations (BMTs), as these are presently the most common transplantations from live donors. During the work on the report, it became clear to the Council that, apart from problems concerning coercion and commercialization that affected both adult and child donors, by far the largest ethical problems occurred in donations from children.