Savior siblings, parenting and the moral valorization of children.

Philosophy has long been concerned with 'moral status'. Discussions about the moral status of children, however, seem often to promote confusion rather than clarity. Using the creation of 'savior siblings' as an example, this paper provides a philosophical critique of the moral status of children and the moral relevance of parenting and the role that formative experience, regret and relational autonomy play in parental decisions. We suggest that parents make moral decisions that are guided by the moral significance they attach to children, to sick children and most importantly, to a specific sick child (theirs). This moral valorization is rarely made explicit and has generally been ignored by both philosophers and clinicians in previous critiques. Recognizing this, however, may transform not only the focus of bioethical discourse but also the policies and practices surrounding the care of children requiring bone marrow or cord blood transplantation by better understanding the values at stake behind parental decision making.

Preimplantation genetic diagnosis with HLA matching - a way to save a child.

Preimplantation genetic diagnosis can be used to establish a pregnancy with an embryo that is human leukocyte antigen (HLA)-matched to a sibling having a hematological or immunological disease and needing a life-saving bone marrow transplantation. The ethical aspects of this procedure have been discussed intensively. The procedure applies where no unrelated HLA-matching donor is available or when transplantation from an HLA-matching sibling is considered a better solution. It is only offered in a limited number of centers in Europe as this is a challenging procedure. Where both HLA matching and diagnosis of a dominant disease are necessary, only a small proportion of the embryos can be used, and the procedure is not always technically feasible. The clinical pregnancy rate per cycle started is much lower than following normal in vitro fertilization (IVF) due to a high cycle cancellation rate, but the success rate is only somewhat lower when measured per transfer.

Intramedullary spinal cord implantation of human CD34+ umbilical cord-derived cells in ALS.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with marginal therapeutic options. Degeneration of motor neurons in the primary motor cortex, brainstem and spinal cord lead to rapidly progressive paralysis and finally to death due to respiratory failure. As pharmacological therapies have failed to provide sufficient neuroprotective effects in ALS, transplantation of stem or progenitor cells is considered a promising treatment strategy. Cell transplantation approaches in ALS mainly aim to generate a neuroprotective environment for degenerating motor neurons by transplantation of non-neuronal cells, rather than to replace lost motor neurons. We present a 63-year-old male patient suffering from ALS who underwent intramedullary thoracic spinal cord implantation of human CD34(+) umbilical cord-derived haematopoietic progenitor cells with a three-year follow up after transplantation.

[Ethical aspects of preimplantation genetic diagnosis (PGD)]. / Les aspects éthiques du diagnostic pré-implantatoire (DPI).

The controversy surrounding PGD has not abated in recent times. This is especially the case for PGD-based tissue typing, which is used to select a future child who could serve as a stem cell donor for an older sick sibling. We examine three types of ethical argument cited against PGD in general, and specifically against tissue-typing PGD. These arguments focus on the moral status of the early embryo, the eugenics issue, and the charge that the future child is being exploited. We conclude that none of these three arguments is unassailable, and that it is the reproductive freedom of couples considering PGD that should prevail.

Inductive risk and justice in kidney allocation.

How should UNOS deal with the presence of scientific controversies on the risk factors for organ rejection when designing its allocation policies? The answer I defend in this paper is that the more undesirable the consequences of making a mistake in accepting a scientific hypothesis, the higher the degree of confirmation required for its acceptance. I argue that the application of this principle should lead to the rejection of the hypothesis that 'less than perfect' Human Leucocyte Antigen (HLA) matches are an important determinant of kidney graft survival. The scientific community has been divided all along on the significance of partial antigen matches. Yet reliance on partial matches has emerged as one of the primary factors leading blacks to spend a much longer time than whites on the waiting list for kidneys, thereby potentially impacting the justice of the kidney allocation policy. My case study illustrates one of the legitimate roles non-epistemic values can play in science and calls into question the ideal of a value-free science.

Saviour siblings and collective family interests.

In this article, I will explore the ethical concerns arising out of the use of preimplantation tissue typing (PTT) to create saviour siblings. There are two main ethical concerns about the welfare of the child to be born as a result of PTT. The first is whether the child to be born is treated as a commodity, as simply a means to save the life of his or her sibling. The second is whether the child to be born will be harmed as a result of PTT, either physically, psychologically or socially. These two ethical concerns reflect an individualistic approach to the welfare of the child, whose interests are treated as largely separate to the interests of other family members. I will argue that the welfare of the child born as a result of PTT should be conceived more broadly to include not only the child's individual interests, but also the collective interests the child shares with his or her family. I base this broader conception of welfare on the notion of human flourishing, which recognises that the welfare of a child is inextricably connected to the welfare of the intimate collective that is his or her family. The collective interests of intimate family members are particularly relevant in the context of PTT, as the members are engaged in a shared journey to save the life of an ill child.

Searching for otherness: the view of a novel.

The ethical issues concerning the use of PGD (Preimplantation Genetic Diagnosis) to select embryos of a particular HLA (Human Leukocyte Antigen) type are numerous. They arise from the potentially conflicting interests between those of the pre-existing child, the subject of a treatment which may be curative, and those of the sibling to be created, who cannot give consent to the donation, together with the problem of the destruction of potentially healthy embryos. This essay focuses on the web of vulnerabilities affecting the parents, the sick child and the "saviour sibling," while addressing three areas: science, bioethics and literature. The novel My Sister's Keeper, by Jodi Picoult, provides the reader with an in-depth view of the conflicting interests and emotional problems that affect the Fitzgeralds, a family experiencing the pain of seeing one of their children dying while facing the tragic consequences of trying to save this child by having another offspring.

Procreative reasons-relevance: on the moral significance of why we have children.

Advances in reproductive technologies - in particular in genetic screening and selection - have occasioned renewed interest in the moral justifiability of the reasons that motivate the decision to have a child. The capacity to select for desired blood and tissue compatibilities has led to the much discussed 'saviour sibling' cases in which parents seek to 'have one child to save another'. Heightened interest in procreative reasons is to be welcomed, since it prompts a more general philosophical interrogation of the grounds for moral appraisal of reasons-to-parent, and of the extent to which such reasons are relevant to the moral assessment of procreation itself. I start by rejecting the idea that we can use a distinction between 'other-regarding' and 'future-child-regarding' reasons as a basis on which to distinguish good from bad procreative reasons. I then offer and evaluate three potential grounds for elucidating and establishing a relationship between procreative motivation and the rightness/wrongness of procreative conduct: the predictiveness, the verdictiveness, and the expressiveness of procreative reasons.

The dilemma of unintentional discovery of misattributed paternity in living kidney donors and recipients.

PURPOSE OF REVIEW: To discuss the issue of misattributed paternity and highlight the complex implications transplant centers must consider when this unsought information is discovered. Policies should be implemented to guide transplant centers in consistent and ethical treatment of this sensitive issue. Effective policy development will require close examination and transparent discussion by the transplant community. RECENT FINDINGS: Despite the fact that little attention has been given to the discovery of misattributed paternity in the field of transplant, transplant centers do encounter this dilemma. The burden of deciding how to treat the information is significant and reaching consensus can be difficult. Recent findings suggest that policy implementation regarding this issue would help to guide practice for professionals who encounter discovery of this unsought information. SUMMARY: This review explores the complex considerations that must occur when misattributed paternity is unintentionally uncovered in living donor-recipient pairs and recommends that the transplant community pursue policies to guide practice in the treatment of this issue.

The future (r)evolution of preimplantation genetic diagnosis/human leukocyte antigen testing: ethical reflections.

There has been increasing support for combining preimplantation genetic diagnosis (PGD) for specific diseases with a test for human leukocyte antigens (HLA) because the generation of HLA-matched umbilical cord blood cells may save the life of a diseased sibling. To date, this procedure has taken place in the context of conceiving another child--PGD/HLA testing type 1. However, it may well become possible to perform PGD/HLA testing outside this context, that is, to select matched embryos from which embryonic stem cells could be derived and used in cell therapy--PGD/HLA testing type 2. A proactive ethical analysis is needed and is presented in this article. Although PGD/HLA testing type 1 can be morally justified, the risks, pitfalls, and practical limitations of this procedure make it necessary to develop alternative strategies. PGD/HLA testing type 2 may provide an alternative strategy. From an ethical point of view, the controversial issue is that this procedure creates embryos purely for instrumental use. However, given the dominant view that the preimplantation embryo has only limited moral value, this alternative may be as morally justified as PGD/HLA testing type 1.

[Non eligibility criteria for hematopoietic stem cell donors: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Critères de non-qualification des donneurs des cellules souches hématopoïétiques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

The evolution of HLA typing and transplantation techniques makes it easier to identify a donor for hematopoietic stem cell (HSC) transplantation. This activity, strongly regulated by regulatory or normative texts, implies in addition biological, medical, para-medical and sometimes psychological evaluations. The benefit/risk discussion is complicated because it must take into account the benefit/risk ratio for the recipient, and the donor risk. No Evidence-Based Medicine data is available and serious events are very rare situations. Biovigilance declarations and their analysis are of fundamental importance. Certain obvious and definite contraindications could be detected very early in the process. It is important to assess whether a risk factor or pathology contributes to increasing the risk associated with collection. In case of recipient risk, the situation should be discussed with the patient team. These recommendations focus on adult peripheral blood HSC donors. They refer to donor information, confidentiality of exchanges, the impact of moral or material pressures, declarations of biovigilance, collegiality and traceability of difficult decisions, desirable experience and training for doctors in charge, use of expert advice informed by an explicit exchange on the possible risks, parsimony of therapeutic interventions and minimization of risks for the donor. We also recommend creation, availability and use by the community of tools and documents (registries, questionnaires, synthetic recommendations, feedback, and collegial qualification meetings) useful for practice.

Pre-implantation HLA matching: The production of a Saviour Child.

Pre-implantation genetic diagnosis (PGD) requires the use of assisted reproductive technology (ART) to create several pre-implantation-stage embryos, followed by biopsy of embryonic cells for genetic testing and transfer of selected embryos to the womb to establish a pregnancy. HLA typing of ART-created embryos was first reported in 2001. The aim is to establish a pregnancy that is HLA-compatible with an affected sibling who requires haematopoietic stem cell transplantation. HLA-typing can be performed with or without PGD for the exclusion of a single-gene disorder. Haematopoietic stem cells collected from the umbilical cord blood or the bone marrow of the HLA-matched donor sibling born, or a combination of both sources, are used for transplantation and cure of the affected sibling. The procedure is multistep and technically challenging. All specialists involved must aim to adequately support and counsel prospective parents. Results have so far been encouraging, with many documented positive outcomes of affected children being cured.

Fetal HLA typing in beta thalassaemia: implications for haemopoietic stem-cell transplantation.

Stem-cell transplantation can cure beta thalassaemia. We aimed to assess whether fetal HLA typing done early in the pregnancy of couples who were at risk of beta thalassaemia could provide an alternative to pregnancy termination if the prospect of a bone-marrow transplantation from a family member was available. In our clinic in Sardinia, we did fetal HLA typing for 49 couples at risk of having a baby with beta thalassaemia. Two affected children were born and successfully received a transplantation from a family donor. Five non-affected fetuses were HLA compatible with an affected sibling and their cord blood was harvested for a future transplantation.

Lives to save lives--the ethics of tissue typing.

Should we allow tissue typing of in vitro embryos in order to implant those which could provide potentially life-saving cells to an existing serious ill sibling with that tissue type? A case is made that such tissue matching does not involve unacceptable instrumentality towards or commodification of children. The key distinction is that the parents' request for tissue typing is reactive in the face of serious medical need rather than being proactive in the sense of seeking the means to specify a child with chosen desirable characteristics. Nevertheless, as preimplantation genetic diagnosis (PGD) is a relatively new technique, both long-term safety issues concerning effects on child development following embryo biopsy and the risks of misdiagnosis must be given due weight as must the avoidance of exploitation of couples desperate to save a sick child. The HFEA originally made a distinction, recently revoked, between allowing tissue typing after PGD to select against affected embryos and denying it when PGD is not required because the embryos are not at risk of inheriting the disease suffered by the existing sibling. If tissue typing is not inherently unethical and misdiagnosis poses a greater risk than biopsy damage, then this distinction is not ethically tenable.

[Preimplantation genetic diagnosis in order to choose a saviour sibling]. / Le diagnostic préimplantatoire en vue de choisir un enfant sauveur de fratrie.

Preimplantation genetic diagnosis with HLA matching in order to bring about the birth of a saviour sibling is not mere instrumentalisation of the future child, as long as the post natal test is used and the future child will be looked after with the same love and care as if he/she had not been selected as well for the purpose.

["Designer baby" changed to French for "double hope baby"]. / Du "bébé médicament" au "bébé du double espoir".

Scientific advances during the last decades regarding potential intervention on embryos arouse many questions in society to prepare the ground concerning the limits that should be set for these practices. For the first time in 1994, a parliamentary proceeding allowed the definition of a French model of bioethics through laws of the same name. These laws, among others, authorized in a well and strictly defined setting the practice of preimplantation genetic diagnosis (PGD). Because of technical progress concerning PGD, new questions arose, especially concerning the accomplishment of designer babies. The French Chamber of Representatives came in with a new law that banishes the concept of designer babies and replaces it with another concept: double hope babies, in French "bébé du double espoir". A first hope of a pregnancy giving birth to a healthy child and the second being that this child conceived with the aid of PGD could help treat an elder brother. Because of the issuing of two specific laws in a ten years interval, France occupies a privileged place in a Europe where bioethical issues continue to be debated, particularly PGD.

[Extending preimplantation genetic diagnosis to HLA typing: the Paris experience]. / Le diagnostic préimplantatoire couplé au typage HLA: l'expérience parisienne.

Preimplantation genetic diagnosis (PGD) consists in the genetic analysis of one or two cells. These cells (blastomeres) are sampled from embryos, obtained by in vitro fertilization, at the third day of development. Since 1998, the bioethical laws (1994) and their decrees restricted PGD practices in France, strictly to the avoidance of the birth of a child affected with a genetic defect. In parallel, works on blood cord transplantation, taken at the birth of a compatible HLA sibling, showed very encouraging results, particularly for the treatment of Fanconi anemia. In 2001, Verlinsky et al., have reported the first PGD for Fanconi anaemia combined with HLA typing, allowing the birth of a healthy child, HLA-identical with his affected sister. The "designer baby" concept was born. The French law, which allowed PGD under specific conditions, i.e. when the genetic defect has been characterized in one parent at least, recently extended PGD to HLA typing when embryos are at risk of a genetic disorder. Article L.2131-4-1 (August 2004) allows the practice of HLA typing for PGD embryos when an elder sibling is affected with a genetic disorder and need stem cell transplantation. The HLA-matched offspring resulting from PGD can give cord blood at birth to supply the necessary therapy. This double selection give rise to serious ethical problems, but technical difficulties and legal restrictions will probably limit the development of such a procedure.

Human reproductive technologies and the law: a select committee report.

The House of Commons Science & Technology Committee has reviewed the Human Fertilisation and Embryology Act. It considered a) the balance between legislation, regulation and reproductive freedom; b) the role of Parliament in human reproductive technologies; and c) the foundation, adequacy and appropriateness of the ethical framework for legislation. It also considered the Act itself and the workings of the Human Fertilisation and Embryology Authority. Its report is written from a very liberal perspective, but is a very thorough overview of current issues and debate in the field. There follow, slightly abridged, the conclusions and recommendations of the 200-page report.

R (on the application of Quintavalle) v Human Fertilisation and Embryology Authority.

KIE: Court Decision: [2005] 2 All England Law Reports 555; 2005 Apr 28 (date of decision). The House of Lords affirmed the Court of Appeal, which held that both pre-implantation genetic diagnosis and HLA typing of an embryo may be used to determine the suitability of an embryo for transfer, as determined by a particular mother. The mother in this case wished to use in vitro fertilization to conceive a child that could be a compatible stem cell donor for her son who suffered from beta thalassemia.^ieng