IVF NewsArticle: Saviour embryos? Preimplantation genetic diagnosis as a therapeutic technology
RBM Online 15 May 2010
Robert Sparrow a,*, David Cram b a Centre for Human Bioethics, Faculty of Arts, Monash University, Vic. 3800, Australia; b Monash Immunology and Stem Cell Laboratories, Faculty of Medicine, Nursing and Health Sciences, Monash University, Vic. 3800, Australia * Corresponding author. E-mail address: [email protected] (R Sparrow).
Dr Sparrow is a Senior Lecturer in the School of Philosophy and Bioethics, and the Centre for Human Bioethics, at Monash University. His current research interests include the ethics of human enhancement, the ethics of preimplantation genetic diagnosis, and the ethics of xenotransplantation. AbstractThe creation of ‘saviour siblings’ is one of the most controversial uses of preimplantation genetic diagnosis (PGD). This paper outlines and invites ethical discussion of an extension of this technology, namely, the creation of ‘saviour embryos’ to serve as a source of stem cells to be used in potentially life-saving therapy for an existing child. A number of analogies between this hypo- thetical use of PGD and existing uses of IVF are offered and, in addition, between saviour embryos and proposed therapeutic appli- cations of stem cell technology. The ethical significance of a number of disanalogies between these cases are explored and investigated. While the creation of saviour embryos would involve a significant shift in the rationale for IVF and PGD, it is suggested here that the urgent need of an existing individual should be prioritised over any obligations that might exist in relation to the cre- ation or destruction of human embryos. RBMOnline © 2009, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. KEYWORDS: embryos, ethics, IVF, PGD, saviour siblings, stem cells IntroductionThe creation of ‘saviour siblings’ is one of the most controversial uses of preimplantation genetic diagnosis (PGD). In rare circumstances, the only way to save the life of a child may be to use PGD to facilitate the birth of another child who can serve as a donor of matching tissue (Kuliev et al., 2005, Samuel et al., 2008, Verlinsky et al., 2007). In rarer circumstances still, the parents of a child suffering from a life-threatening illness and requiring a donation of a rare tissue type may be capable of producing embryos but not of bringing a child to term. As a result, such couples do not have the option of creating a saviour sibling. However, recent advances in our knowledge of stem cells and understanding of processes of cellular differentiation have opened up the possibility of deriving specific cell types from embryonic stem cells (Bhatia, 2007, Murry and Keller, 2008, Ng et al., 2005). If the couple could conceive and identify an embryo with the appropriate tissue type using IVF and PGD, it might then be possible to extract stem cells from that embryo and then differentiate them into the cells required for transplant into their existing child in order to save his or her life. This scenario might be thought of as involving the creation of ‘saviour embryos’. Because the creation of saviour embryos would involve the deliberate creation of embryos with the intent to destroy them, it is likely to prove extremely controversial. However, it is also likely to be a life-saving technology for young children in some circumstances and, as such, is clearly worthy of serious discussion. This paper invites comment and discussion from medical ethicists in order to guide future thinking and practice in relation to this proposal. To facilitate this discussion, a number of analogies between this hypothetical use of PGD and existing uses of IVF are offered and also between saviour embryos and proposed therapeutic applications of stem cell technology. The ethical significance of a number of disanalogies between these cases are also explored and investigated. While the creation of saviour embryos would involve a significant shift in the rationale for PGD, it is suggested here that the urgent need of an existing individual should be prioritised over any obligations that might exist in relation to the creation or destruction of human embryos. The case for saviour embryosThere are a number of diseases affecting children, including Fanconi anaemia, beta thalassaemia, sickle cell disease and some immunodeficiencies, where the only treatment that will save the life of the child involves a transplant of tissue from a human leukocyte antigen (HLA)-compatible donor (Lucarelli et al., 2002, Verlinsky et al., 2001, Verlinsky et al., 2007). In cases where it has proved impossible to locate a suitable donor, some parents have chosen to conceive another child in the hope that this child – a so-called ‘saviour sibling’ – will be able to serve as a tissue donor to save the life of the existing child (McBride, 1990, Robertson et al., 2002). More recently, PGD has been employed to ensure that the child that will be born will be capable of serving as a source of matched tissue (Kuliev et al., 2005, Samuel et al., 2008, Verlinsky et al., 2001, Verlinsky et al., 2007). If the parents of a terminally ill child are unable to find a suitable donor and are also unable to have another child due to the woman’s inability to carry another child to term, currently their only hope of saving the life of their child would be to try to secure the services of a surrogate mother to bear a child conceived of their gametes, which then might serve as a saviour sibling. This may prove extremely difficult: in some jurisdictions surrogacy may not be legal; even where surrogacy is legal, the parents may not be able to find a willing surrogate. However, recent advances in stem cell science suggest another possibility. It seems likely that, in the not-too-distant future, it will be possible to derive specific tissues from embryonic stem cells and then use these for therapies, including transplants of the sort necessary to save the lives of children in the situation described above (Daley and Scadden, 2008, Lerou and Daley, 2005, Murry and Keller, 2008). Should this become the case, then parents might conceive a number of embryos using IVF and screen them for HLA-compatibility with the existing child using PGD. Stem cells from a compatible embryo might then be used to derive tissue for transplant to save the life of their existing child. The embryos created – and destroyed – in this process would be ‘saviour embryos’. The need for saviour embryos may lapse if it proves possible to derive suitable tissue for the appropriate transplants from embryos created using somatic cell nuclear transfer (SCNT) of DNA from a person who was HLA-compatible with the child requiring a transplant (Elsner, 2006, Vanikar et al., 2007) or from ‘induced pluripotent stem (IPS) cells’ created from such a person (Baker, 2007, Takahashi et al., 2007, Yu et al., 2007). The latter technology would clearly be preferable, if it becomes available, as it would avoid the creation of a human embryo (some ethical concerns about SCNT cloning are discussed below). However, both these alternative solutions to the problem faced by parents of children requiring tissue-matched stem cell transplants are (also) hypothetical. It may be that the challenges involved in developing a procedure to clone and reliably derive stem cells from human blastocysts (Hall et al., 2006) or in demonstrating the safety of transplants from tissues derived from IPS cells (Daley and Scadden, 2008, Zhao and Daley, 2008) means that these alternatives will not become available for some years after the date at which it becomes possible to safely transplant tissue derived from embryonic stem cells. For some period at least, then, it may be that the creation of saviour embryos would be the only way to save particular human lives. Because the circumstances described above will be rare, the proportion of those people requiring an HLA-compatible transplant who could only be saved by the creation of a saviour embryo is likely to be small. However, the number of people affected by diseases that are best treated by a transplant from an HLA-compatible donor is large, with over 330,000 affected children being born each year, according to some estimates (Modell and Darlison, 2008). There are therefore a significant number of patients who could benefit as a result of the creation of saviour embryos. Moreover, every life is precious and in cases of the sort described above, children will die unless their parents are allowed – and assisted – to create saviour embryos. There is thus a compelling prima-facie case for the creation of saviour embryos in at least some circumstances. This case is established by the moral weight of the urgent medical need of a living individual and the desperate desire of parents to save the life of their child. The most obvious objections to the proposal presented here arise out of a concern for whatever moral respect is due to the embryos that would be destroyed during the course of this procedure. Obviously, it is not possible to settle the vexed question of the moral status of human embryos in this context. However, it is worth emphasizing the burden of the argument required to establish that the embryos that would be destroyed in this procedure are worthy of a moral respect sufficient to render the procedure unethical. At the time at which stem cells would be removed from the embryo, the embryo consists of a ball of 80–100 cells. It has no nerve cells, is incapable of experiencing any sensation, and has no desires; thus destroying it will not cause it any suffering or frustrate any preferences (Singer, 1999, Tooley, 1999). If implanted into a woman’s womb, the embryo might develop into a child, but equally well it might not, as many embryos which succeed in implanting do not go to term. The moral significance of any potential the embryo does have is unclear. As John Harris (Harris, 1998) has pointed out, all living human beings are potential corpses but that doesn’t mean that living persons should be treated as though they were dead. Moreover, because of the possibility that these early-stage embryos may undergo spontaneous fission up until 14 It is true that even such early-stage embryos do represent the beginning of human life (if not necessarily one single human life) and are consequently an important ‘symbol’ of a human life (Dworkin, 1993, Robertson, 1995, Steinbock, 2003). In other circumstances, such embryos are the focus of their parents’ hopes and dreams and are treated as objects of great value. For these and other reasons, human embryos should be treated with a degree of respect that is not required in the treatment of other human cells or animal embryos (Steinbock, 2003). It is far from clear, however, that such respect is incompatible with the destruction of embryos if the reasons for the destruction are sufficiently morally weighty (Robertson, 1995, Steinbock, 2003). The urgent need to save the life of a sick child would seem to be just such a morally weighty reason. Of course, there is a significant constituency amongst those involved in bioethical debate that will find these arguments about the (lack of) moral status of early-stage human embryos unconvincing. It may prove that no amount of philosophical argument will be sufficient to convince those who believe that embryos have the same moral status as innocent adult human beings that the destruction of embryos is ever warranted, especially where this conviction is founded on the authority of religious texts (Congregation for the Doctrine of the Faith, 1987). However, as shall be demonstrated below, those who are prepared to contemplate the destruction of embryos in any circumstances at all may be invited to consider the relationship between those circumstances and the technology proposed here. In this way it may be possible to make some progress in relation to the ethics of saviour embryos without needing to resolve more fundamental differences in opinion about the moral status of embryos. Analogies?While, at first sight, what is proposed here may seem to involve a radical extension of existing medical practice, careful consideration of a number of analogies with medical practices that are widely, if not universally, accepted suggests that the creation of saviour embryos may raise fewer ethical dilemmas than first appears. Natural conceptionPerhaps surprisingly, one of the most compelling analogies between this proposal and existing reproductive practice is the analogy with natural conception. If any reproductive practice is ethical, then presumably reproduction as a result of natural conception, pregnancy, and birth is ethical. Yet natural conception does not guarantee that those embryos that are conceived will come to term. A significant percentage of embryos, up to 33% according to some authorities, will be spontaneously aborted before pregnancy or at some stage of the pregnancy (Modvig et al., 1990). A willingness to conceive naturally therefore requires that the couple be prepared to sacrifice those embryos that may be spontaneously aborted in the course of the attempt to become pregnant for the sake of the life of the child that is eventually born (Harris, 2006, Harris, 2007). In fact, even this description exaggerates the moral weight of the justification for the destruction of embryos that occurs naturally. While, in those circumstances in which a pregnancy is planned, the parents intend the birth of a child, they are unable to justify this with reference the child’s benefit: as the child does not exist at the time at which this decision is made, the child may neither be harmed nor benefitted. Instead, parents’ reasons for wanting a child necessarily refer to the desires of existing persons, to have a family, to experience the joys of parenthood, to express their love for each other, or to provide a companion for an existing child. While these may be admirable desires, they do not seem to have as much weight as the desire to save the life of an existing child. Moreover, of course, many pregnancies are not planned and result instead from contraceptive accident, risk taking, passion, intoxication, or ignorance. In such cases, embryos are created and consequently often destroyed (when they fail to implant or miscarriage occurs) for reasons which are at best morally trivial and are often reprehensible. Both natural conception and the creation of saviour embryos require a willingness to sacrifice embryos to serve the desires of existing persons. The reasons for the creation and destruction of saviour embryos are prima facie more morally compelling than the reasons for the creation and destruction of embryos in natural conception. As natural conception is – presumably – ethical, this suggests that the creation of saviour embryos would also be ethical. Of course, the pursuit of natural conception only requires a willingness to risk the destruction of embryos whereas the destruction of embryos is required by the application of saviour embryos. However, the risk of the destruction of embryos that is involved in natural conception is converted into a virtual certainty in another reproductive technology – in-vitro fertilization. In-vitro fertilizationBecause of the costs, discomforts, and risks involved in each cycle of IVF and because the rate of successful pregnancies per embryo conceived is still low, IVF laboratories will usually create multiple embryos. These embryos will then be screened according to the IVF technician’s estimation of how likely they are to lead to a successful pregnancy, with the ‘best’ embryos first to be implanted into the womb of the woman who wants to become a mother. Once a pregnancy is secured, the remaining embryos will normally be discarded. IVF therefore requires a willingness to create multiple embryos knowing that most of them will not be implanted and will eventually be destroyed (Devolder, 2005a,Harris, 2006, Shannon and Cahill, 1988, Singer and Wells, 1984). Moreover, while the screening involved in IVF is usually thought of as ‘screening in’ for implantation, it might equally well be thought of as ‘screening out’ embryos that are thereby unlikely to be implanted. These embryos are thus effectively ‘selected for destruction’ for the sake of securing a pregnancy leading to the birth of a(nother) child. This process arguably further instrumentalizes the embryos that are destroyed in the process (Shannon and Cahill, 1988). Finally, it is also the case in IVF that, after a pregnancy has been secured, it can be said that each embryo that was not implanted was created for the sake of another child. Like the creation of saviour embryos, IVF involves the destruction of embryos, the selection of embryos for destruction, and the creation of embryos in the knowledge that they are likely to be destroyed. IVF is dedicated to bringing a child into the world, whereas the proposal under discussion would be aimed at saving the life of an existing child. If IVF fails, the desires of the parents are frustrated but no other individual is harmed; on the other hand, without the creation of a saviour embryo, a child will die. Again, the justification for the way embryos are treated in the creation of saviour embryos seems significantly greater than that for the same treatment in IVF. However, it remains true of each individual embryo that is created in IVF, that it is created with the intention of bringing a child into the world (FitzPatrick, 2003). This is not true of this paper’s proposal, which involves creating human embryos with no intention of allowing them the opportunity to flourish. Another technology that would also involve the creation of embryos for a purpose which requires their destruction, therapeutic cloning, is discussed below. First, however, a number of other reproductive technologies that have elements in common with this paper’s proposal are explored. Preimplantation genetic diagnosisPreimplantation genetic diagnosis extends the screening involved in ordinary IVF to the genetics of the embryos created in order to increase the chances that a child will be born healthy. Again, PGD will typically involve screening out undesirable embryos rather than screening in desirable embryos – although this distinction is not always clear given that screening out undesirable traits will also be screening in desirable traits (Silver, 1999). PGD will also involve the destruction of those embryos that are not selected for implantation. Whereas the creation of surplus embryos might be said to be an unintended consequence of IVF, brought about by the low rates of implantation of embryos, the creation of multiple embryos, most of which will subsequently be destroyed, is an essential part of PGD, which aims to select one embryo from amongst many. Moreover, when the procedure is initiated there is the intention that particular (sorts of) embryos, if detected, will not be implanted and will therefore be destroyed. It is this feature of PGD that has been singled out for criticism by some activists within the disability community on the grounds that PGD necessarily involves the belief that it would be better if disabled people did not exist (Asch, 1988, Asch, 2000, Kaplan, 1993, Saxton, 1998, Wendell, 1996). If PGD is ethical then presumably not only the destruction of embryos but also the creation of ‘excess’ embryos, and the selection of embryos for destruction are ethical, and thus the presence of these elements in the creation of saviour embryos should not rule it out. Nonetheless, like IVF, PGD only involves the destruction of embryos as a foreseen but unintended consequence of the pursuit of a healthy baby. The procedure under investigation would require the destruction of an embryo and, as such, this would be an intended consequence of the procedure. However, the widespread availability of another reproductive technology – abortion – suggests that such destruction may sometimes be ethical. AbortionAbortion is legally available in many polities and widely practiced even in those polities where it is not legal. It is difficult to see how those who accept the moral permissibility of abortion in any circumstances could object to the destruction of embryos involved in the production of saviour embryos. Insofar as abortion would usually be procured for a reason, the embryo might be said to be destroyed for the sake of this reason. Yet the reasons for abortion usually fall well short of the need to save the life of an existing child that might justify the creation of saviour embryos. Unfortunately, in the context of debates around the proper treatment of human embryos, abortion is likely to be just as controversial as the creation of saviour embryos and so arguments by analogy from the moral permissibility of abortion will have limited traction when it comes to convincing critics of the destruction of embryos involved in making saviour embryos that such destruction is warranted. However, the analogy with abortion is worth mentioning because a significant percentage of persons do believe that abortion may sometimes be justified and thus that the destruction of embryos may sometimes be justified. If the destruction of embryos is ever justified, it seems it would be justified in the scenario envisioned here. Of course, the justification (or otherwise) of abortion is only relevant to the ethics of the destruction of embryos, whereas the procedure imagined here would also involve the creation of embryos for the sake of saving the life of another child. The next analogy to explore therefore is the analogy with saviour siblings. Saviour siblingsThe creation of saviour siblings has been the topic of extensive ethical debate, with a number of authorities concluding that it is in fact ethical (Damewood, 2001,Devolder, 2005b, Fost, 2004, Ram, 2006, Robertson et al., 2002, Sheldon and Wilkinson, 2004). It is also legally permissible in a number of jurisdictions (Ram, 2006,Spriggs and Savulescu, 2002). The main difference between the creation of saviour embryos and the creation of saviour siblings is that the latter involves the creation of a human child and not just of an embryo. After an embryo with an appropriate tissue type has been selected using PGD, this embryo is then implanted into the womb of a woman with the intention of extracting some of the child’s tissues (usually bone marrow or umbilical cord blood) for the purpose of transplant into a terminally ill child (Verlinsky et al., 2001. Early examples of the pursuit of a matching tissue donor were relying on brute luck to ensure that the child born could serve as a donor for an existing child (Ram, 2006) but the use of PGD maximizes the chance that the child born will be an appropriate source of tissue and minimizes the chances that multiple children might need to be brought into the world in order to achieve this result. Because the creation of a saviour sibling will usually require the creation of multiple embryos for the sake of PGD, it will also involve the destruction of embryos and the creation of embryos knowing that most of them will be destroyed. However, in contrast with the hypothetical creation of saviour embryos, all of the embryos created in the process of creating a saviour sibling are conceived with the intention of bringing a child into the world. Of course, this is not the only intention involved in the creation of saviour siblings, as the procedure is initiated with the intention of thereby saving the life of the already existing child. The presence of this ‘other’ intention has led critics of this procedure to argue that it involves ‘instrumentalizing’ the child that is created by bringing it into existence as a means to the end of saving another child’s life (King, 2006, McBride, 1990, Sutton, 2004). Defenders of saviour siblings have responded that the Kantian injunction against instrumentalizing human beings prohibits the treatment of others solely as a means to an end and that the creation of a saviour sibling does not involve this because the parents of the child that is born will inevitably also love this child for its own sake (Boyle and Savulescu, 2001, Devolder, 2005b, Sheldon and Wilkinson, 2004). The significance of this claim is in turn tendentious because, while it may be true that parents will love the saviour sibling, it is in many cases less clear that they would have had this child were it not for the desire to source tissue for transplant; consequently, in making the decision to conceive a child they may well have been doing so solely as a means to an end. If the creation of saviour siblings is ethical, it must be the case that the creation of human embryos for the purpose of saving a life of an existing child is ethical – although this in itself does not settle the further question of the ethics of creating embryos with no intention of creating a living child. However, if the objection to the treatment of the beginnings of human life in the hypothetical creation of saviour embryos relates to the instrumentalization of human beings then it might be argued that it is in fact preferable to instrumentalize an embryo rather than a child. Any child born as a result of the need for a saviour sibling will grow up with the realization that they were conceived for the sake of making tissue for transplant; the circumstances of their conception may have psychological consequences (King, 2006, Sutton, 2004). This will not be the case with the creation of saviour embryos where, if instrumentalization occurs, it occurs without any consequences for any particular person. In this important regard, the creation of saviour embryos is arguably more ethical than the creation of saviour siblings. The fundamental disanalogyThis paper has identified multiple analogies between the ways in which embryos are treated in and by existing reproductive technologies and the proposed creation of saviour embryos. Yet none of the technologies surveyed thus far contains all of the elements involved in the creation of saviour embryos. Moreover, the creation of saviour embryos would involve the creation of an embryo with no intention of bringing a child into the world – a feature shared by none of these other reproductive technologies. Indeed, strictly speaking, while it would involve the creation and manipulation of human embryos, the creation of saviour embryos would not be a reproductive technology at all. Instead, it would involve the use of IVF as a ‘therapeutic’ technology. This represents the most profound ethical challenge posed by the creation of saviour embryos: is it ethical to treat human embryos as a resource to be exploited rather than – or as well as – as the beginning of a (potential) human life (FitzPatrick, 2003)? Posing the ethical question in this way dramatizes the shift in the justification for the creation of embryos involved in the production of saviour embryos. However, it is worth immediately noting three things. Firstly, while this procedure would use embryos, it would use them for the sake of saving a human life, a project which, as noted above, is more morally praiseworthy than many of those in which embryos are created and destroyed (Fost, 2004, Harris, 2006): the presence of an instrumental attitude should not be taken to exclude the existence of a virtuous intention. Secondly, further argument would be required to show that this shift in attitude towards embryos would lead to any change in attitudes towards children or adults. Assertions of a ‘slippery slope’ need to be backed up by a plausible account of the causal mechanism leading to the repugnant result (Burgess, 1993, Sheldon and Wilkinson, 2004, Williams, 1985). They also need to be sensitive to empirical data about the degree to which the anticipated changes have occurred in other, relevantly similar, circumstances. This latter observation is important because, thirdly, to an extent, this change in the status of (some) embryos has already happened – at least in those jurisdictions where embryos are used for research. It also seems likely that, in the not-too-distant future, other therapeutic technologies involving embryos may be developed. Further analogiesConsequently, three further analogies may productively illuminate the ethics of the creation of saviour embryos. The first involves the destruction and use of embryos in projects other than that of bringing a child into the world. The second involves the hypothetical creation of a child via IVF with the intention of using the surplus embryos created in this process as saviour embryos. The third involves the creation of embryos for therapeutic purposes. Use of ‘surplus’ embryos post-IVFAs noted above, IVF will typically involve the creation of multiple embryos but only the implantation of a small subset of these. The majority of couples undergoing IVF will therefore be left with a number of frozen embryos after they have succeeded in having a child. The question of what to do with these ‘surplus’ embryos has been one of the most controversial and vexed ethical issues surrounding IVF (de Lacey, 2007, Singer and Wells, 1984). In a number of jurisdictions, including Australia, the option is now open to couples to make these embryos available to scientists for use for research (Knowles, 2004, Research Involving Human Embryos Act, 2002). The argument for this practice is compelling: as these embryos are going to be destroyed anyway it seems preferable that their existence should contribute to the possibility of improving human wellbeing in the future (Devolder, 2005a, Harris, 2006, Savulescu, 2000). In so far as the use of embryos for research purposes is ethical, their use for therapeutic purposes would also seem to be ethical given that the latter would, ex hypothesi, result in an immediate and concrete benefit to identifiable human beings whereas the former involves only the possibility of some future benefit. However, it remains the case that research on surplus embryos involves using embryos that already exist rather than creating them for this purpose. Before leaving this analogy, though, it is worth noting that the existence of surplus IVF embryos opens up the possibility of deriving cell lines for therapy without needing to create saviour embryos. For instance, if the couple who had a sick child had already undergone IVF they might be able to find a tissue match with one of their existing surplus embryos. They could then consent to the destruction of this embryo for the purpose of deriving stem cells and then the appropriate cell lines from it to use to save the life of their sick child. Given that this embryo would otherwise be destroyed – and especially if the parents have the right to donate the embryo for destructive research – it is difficult to countenance any objection to this procedure. Perhaps slightly – but only slightly – more controversially, the parents of the child requiring a transplant could seek the help of other couples who had undergone IVF and who had surplus embryos to see whether a tissue match could be found with any existing embryo anywhere. Again, as long as the appropriate consent was secured from those responsible for the embryo, it seems as though deriving cell lines to save the life of an existing child, from an embryo that would otherwise be destroyed, would be ethical. Saviour donated siblingsIf the use of surplus embryos for therapeutic purposes is ethical, the possibility arises that the parents of a child requiring a stem cell transplant might arrange to provide an embryo to another couple in need of a donor embryo for reproductive purposes and undergo IVF and PGD in order to do so, in the hope that any surplus embryos created could serve as a source of tissue for their existing child. They would therefore enter the IVF programme with the intent to conceive a child. Once the other couple had secured the birth of a child using one of the embryos that the parents of the sick child had created, the parents of the sick child could then consent to allow their remaining embryos to be used for ‘research’ into the derivation of stem cells. If this derivation is successful, the parents of the sick child could then hope that these tissues might be used in therapy to save the life of their child. In such a scenario, the child born as a result of the donation could then be said to be a saviour sibling to the sick child, although the cells used to save the life of the sick child would in fact been derived from another embryo. Of course, if the parents can find another couple willing to have a child conceived of their gametes, they might equally well request that PGD be used to ensure that this child could serve as a tissue-matched donor to save the life of their child – in which case there would be the creation of a saviour sibling born to a couple who are not the genetic parents of the child. To generate the precise scenario envisioned here, it would therefore have to be the case either that the tissues required for transplant could not be sourced except from embryonic stem cells or that the embryo donors could not rely upon the birth parents to consent to allow the child to serve as a tissue donor. In any case, the interesting question about this scenario is not whether or not it would be the only or the best way to achieve the parents’ goals but whether or not each individual step in the process described would be ethical. Note that in the above scenario, all the embryos conceived are created with the intention of bringing a child into the world. This procedure would therefore avoid objections based on the moral impermissibility of the deliberate creation of embryos for the purposes of destroying them. Note also that the couple seeking a donated embryo have a more plausible case that they will love the resulting child for its own sake than the parents of ordinary saviour siblings. The creation of saviour donated siblings in this scenario therefore appears to be more ethical than in the ordinary case of the creation of saviour siblings. It seems, therefore, that a compelling case could be made for this course of action: the creation of a ‘saviour donated sibling’. Nevertheless, it is hard to avoid the suspicion that, at some level, the distinction between this scenario and the creation of saviour embryos is casuistry. If the therapeutic use of tissue derived from embryos is sometimes ethical, it is difficult to see how whether it is ethical or not could depend on whether or not another child had been born as the result of the process in which the embryo was created. Therapeutic cloningBioethicists have already extensively discussed an arguably much more powerful technology, which is related to the one under investigation here. ‘Therapeutic’ cloning would involve using somatic cell nuclear transfer to create a blastocyst from which to derive embryonic stem cells and then specific cell types that were genetically identical to the cells of the person being treated for transplant or other therapies. As noted earlier, recent advances in the creation of induced pluripotent stem cells suggest that it may eventually be possible to derive patient-specific stem cells for therapeutic purposes from somatic cells without the need to involve a human ovum or to create a blastocyst, in which case the justification for therapeutic cloning would lapse. However, what is important for the purposes of the argument here is the fact that numerous discussions of the possibility of therapeutic cloning have argued that it would be justified if it offered real therapeutic benefits. Therapeutic cloning might be argued to be more ethical than the creation of saviour embryos on the grounds that it does not involve conceiving new embryos by fusing spermatozoa and eggs but only involves making copies of a genetic blueprint that already exists and could be further copied as required. However, this intuition relies on a misconception that genetically identical embryos would grow up to be the ‘same’ person. The creation (or destruction) of cloned embryos is no different to the creation (or destruction) of ordinary embryos – at least as far as the moral status of the embryos is concerned (Savulescu, 2000). Identical twins do not have a lesser moral status by virtue of being clones; neither should embryos which are genetically identical to each other or to an existing person. Thus, like the creation of saviour embryos, therapeutic cloning would involve the creation of embryos with the intention of using them for therapeutic purposes. If therapeutic cloning would be ethical, so too would be the creation of saviour embryos. Of course, those who object to the creation of embryos for purposes that would involve destroying them are unlikely to hold that therapeutic cloning would be ethical, so, as was the case with the observations above about abortion, the argumentative traction of this analogy with those entirely opposed to the instrumental use of embryos may be limited. Nevertheless, the analogy with therapeutic cloning does establish that the creation of saviour embryos would be no more radical a step than another proposed technology with numerous defenders and substantial popular support (Devolder and Savulescu, 2005, Savulescu, 2000, Tooley, 2006). ConclusionThis paper has explored multiple analogies between the proposed creation of saviour embryos and existing reproductive technologies, which productively illuminate the ethical issues involved. With the exception of the deliberate conception of embryos for purposes that would involve destroying them, all of the other controversial aspects of the treatment of embryos in this procedure may be found in existing reproductive technologies that are widely believed to be ethical. However, endorsing saviour embryos would significantly transform the rationale for IVF in such cases, rendering it a therapeutic technology. It would also involve the instrumentalization of human embryos. In both of these regards, though, the creation of saviour embryos is akin to the proposed creation of cloned embryos for therapeutic purposes. These proposals should therefore stand or fall together. Moreover, it is possible that the creation of saviour embryos will offer the possibility of saving lives significantly sooner than therapeutic cloning. Finally, there exists a plausible set of actions and intentions that would allow the therapeutic use of an embryo deliberately created for the purpose as long as another child was born as a consequence. If this is casuistry, as suggested herein, then it may be necessary to rethink the ethics of donation of embryos for research or our objections to the therapeutic use of embryos. It is very likely that, if the technology to derive useful tissues from embryonic stem cells arrives before a safe way of deriving the same tissues from somatic cells, (some) desperate parents will demand to be allowed to create saviour embryos. Where the lives of children are at stake, it will be difficult to resist this call unless there is a clear consensus that this procedure would be unethical. Yet the deliberate creation of the first stages of human life for purposes which require their destruction is likely to be extremely controversial. It is therefore vital that medical ethicists should begin discussing these possibilities now. The authors hope that this article may serve as a useful starting point for this process. AcknowledgementsThanks are due to Emilio Mora and Nicole Kouros for the work they performed as a research assistants, which assisted in the preparation of this paper for publication, and to Justin Oakley for helpful comments on an earlier draft. Dr Sparrow would also like to thank Dr Susan Hawes for directing him to appropriate sources in the medical and scientific literature on a number of occasions. ReferencesAsch, 1988. Asch A. Reproductive technology and disability. In: Cohen S, Taub N editor. Reproductive Laws for the 1990s. Clifton, NJ: Humana Press; 1988;p. 69–124. Asch, 2000. Asch A. Why I haven’t changed my mind about prenatal diagnosis: reflections and refinements. In: Parens E, Asch A editor. Prenatal Testing and Disability Rights. Washington, DC: Georgetown University Press; 2000;p. 234–258. Baker, 2007. Baker, M., 2007. Adult cells reprogrammed to pluripotency, without tumors. Nat. Rep. (December 6, 2007). Available from:<http://www.nature.com/stemcells/2007/0712/071206/full/stemcells.2007.124.html> (accessed May 10, 2009). Bhatia, 2007. Bhatia M. Hematopoiesis from human embryonic stem cells. Ann. NY Acad. Sci. 2007;1106:219–222. CrossRef Boyle and Savulescu, 2001. Boyle RJ, Savulescu J. Ethics of using preimplantation genetic diagnosis to select a stem cell donor for an existing person. Br. Med. J.2001;323(7323):1240–1243. Burgess, 1993. Burgess J. The great slippery-slope argument. J. Med. Ethics. 1993;19(3):169–174. MEDLINE | CrossRef Congregation for the Doctrine of the Faith, 1987. Congregation for the Doctrine of the Faith, 1987. Instruction on Respect for Human Life in its Origin and on the Dignity of Procreation: Replies to Certain Questions of the Day. Available from:<http://www.vatican.va/> (accessed November 17, 2008). Daley and Scadden, 2008. Daley GQ, Scadden DT. Prospects for stem cell-based therapy. Cell. 2008;132(4):544–548. CrossRef Damewood, 2001. Damewood MD. Ethical implications of a new application of preimplantation diagnosis. J. Am. Med. Assoc. 2001;285(24):3143–3144. de Lacey, 2007. de Lacey S. Decisions for the fate of frozen embryos: fresh insights into patients’ thinking and their rationales for donating or discarding embryos. Hum. Reprod. 2007;22(6):1751–1758. MEDLINE | CrossRef Devolder, 2005a. Devolder K. Creating and sacrificing embryos for stem cells. J. Med. Ethics. 2005;31(6):366–370. MEDLINE | CrossRef Devolder, 2005b. Devolder K. Preimplantation HLA typing: having children to save our loved ones. J. Med. Ethics. 2005;31(10):582–586. MEDLINE | CrossRef Devolder and Savulescu, 2005. Devolder K, Savulescu JA. The moral imperative to conduct embryonic stem cell and cloning research. Camb. Q. Healthc. Ethics.2005;15(1):7–21. MEDLINE Dworkin, 1993. Dworkin RM. Life’s Dominion: An Argument about Abortion, Euthanasia, and Individual Freedom. New York, NY: Alfred A. Knopf; 1993;. Elsner, 2006. Elsner D. Just another reproductive technology? The ethics of human reproductive cloning as an experimental medical procedure. J. Med. Ethics.2006;32(10):596–600. MEDLINE | CrossRef FitzPatrick, 2003. FitzPatrick W. Surplus embryos, nonreproductive cloning, and the intend/foresee distinction. Hastings Cent. Rep. 2003;33(3):29–36. MEDLINE |CrossRef Fost, 2004. Fost NC. Conception for donation. J. Am. Med. Assoc. 2004;291(17):2125–2126. Hall et al., 2006. Hall VJ, Stojkovic P, Stojkovic M. Using therapeutic cloning to fight human disease: a conundrum or reality?. Stem Cells. 2006;24(7):1628–1637.MEDLINE | CrossRef Harris, 1998. Harris J. Clones, Genes and Immortality: Ethics and the Genetic Revolution. Oxford, UK: Oxford University Press; 1998;. Harris, 2006. Harris J. Stem cells, sex, and procreation. In: Kuhse H, Singer P editor. Bioethics: An Anthology. second ed.. Malden, MA: Blackwell Publishing;2006;p. 545–558. Harris, 2007. Harris J. Enhancing Evolution: The Ethical Case for Making Better People. Princeton, NJ: Princeton University Press; 2007;. Kaplan, 1993. Kaplan D. Prenatal screening and its impact on persons with disabilities. Obstet. Gynecol. 1993;36(3):605–612. King, 2006. King D. Why we should not permit embryos to be selected as tissue donors. In: Kuhse H, Singer P editor. Bioethics: An Anthology. second ed.. Malden, MA: Blackwell Publishing; 2006;p. 158–161. Knowles, 2004. Knowles LP. A regulatory patchwork – human ES cell research oversight. Nat. Biotechnol. 2004;22(2):157–163. MEDLINE | CrossRef Kuliev et al., 2005. Kuliev A, Rechitsky S, Tur-Kaspa I, et al. Preimplantation genetics: improving access to stem cell therapy. Ann. NY Acad. Sci. 2005;1054:223–227.MEDLINE | CrossRef
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News: IVF works well in women under 35, study finds
Katy Sinclair 19 January 2009
Researchers at Harvard Medical School, US, have conducted the largest study ever into IVF live births, using data from Boston IVF and Israel Deaconess Medical Centre, in an attempt to quantify the success rate of IVF in both younger and older women. The findings are published in the New England Journal of Medicine. [ Full Article ]
News: UK IVF success rates and league tables announced
Dr Kirsty Horsey 12 December 2007
New figures, released last week by the UK's Human Fertilisation and Embryology Authority (HFEA), show that the number of women undergoing fertility treatment in the UK is continuing to rise, as are success rates. Data for 2005 shows a six per cent increase in the number of women undergoing IVF treatment, from 30,861 women having a total of 40,164 cycles of IVF in 2004, to 32,626 having 41,932 in 2005. The number of cycles performed increased in that period by 4.5 per cent.
Following those incidences of IVF, there were a total of 9,058 births which, when multiple births were taken into account, meant a total of 11,262 children. The overall 'live birth rate' for all IVF in 2004-5 was therefore 21.6 per cent, an increase from the previous year's figure of 20.6 per cent. For women aged 35 or less, the success rate was even higher, at 29.6 per cent, again an increase on the previous year, where it was 28.1 per cent. In total there were 722,500 babies born in Britain in 2005, meaning that approximately one in every 64 births was from IVF. In the same time period, there were 606 births following donor insemination, resulting in 645 children. 749 children had been born this way in 2003-4, meaning a decrease of 11 per cent. The HFEA said that there may be a reduction in the amount of times donor sperm is needed, with the increase of use of newer treatments such as intra-cytoplasmic sperm injection (ICSI) which mean that the partner's sperm can be used in more cases. Despite this, the figures also showed that the number of men registering as sperm donors has risen, with 307 donors registering in 2006, an increase of 19 per cent from 2005, when only 259 registered. Individual clinic success rates were also released last week. The Assisted Reproduction and Gynaecology Centre in London again had the highest success rate in the country: almost two thirds of patients who were aged under 35 and used their own eggs had a baby in 2005, which was the clinic's best result yet and one of the highest success rates of any clinic in the world. The clinic's live birth rate of 60.7 per cent is twice the national average of 29.6 per cent for this age group. The Lister Fertility Clinic in London came in second, with a rate of 43.1 per cent for women aged 35 and under. Mohamed Taranissi, who runs the Assisted Reproduction and Gynaecology Centre, also came fourth in the league table with the Reproductive Genetics Institute, his other clinic. The HFEA decided in July to strip him of his right to be 'person responsible' for the Assisted Reproduction and Gynaecology Centre after saying that he treated patients at the Reproductive Genetics Institute without a licence, a decision that the Times newspaper said now looks 'embarrassing' for the HFEA. The BBC website (see link below) shows the top ten performers, and the new 'Find a Clinic' guide on the HFEA's website also contains all the information on success rates. [ Full Article ]
News: Melatonin could improve women's IVF success
Harriet Vickers 20 September 2010
Women with poor egg (or oocyte) quality could double their chance of becoming pregnant through IVF if given melatonin, researchers have found. The work was presented at the World Congress of Fertility and Sterility in Munich last week. 'Despite great advances in assisted reproductive technology, poor oocyte quality remains a serious problem for female infertility', said Professor Hiroshi Tamura from the Yamaguchi University Graduate School of Medicine, Japan, who led the research. 'So far no practical and effective treatment for improving oocyte quality has been established'. High levels of oxidising agents - a type of chemical compound - in the follicular fluids surrounding the egg indicate if a woman has low quality oocytes. These can 'stress' and damage the oocyte. The team took one of these agents known as8-OHdG and measured its levels in follicular fluid samples. Levels of melatonin, which is known to have anti-oxidising effects, were also measured. The team found that, as melatonin concentration in the follicular fluids naturally increased, the level of 8-OHdG decreased, leading them to believe melatonin was linked to the reduction of the oxidising agents. They confirmed this finding in mice, and discovered that adding melatonin seemed to reduce the damage to the egg caused by the agents. Next, the group set up a trial with women coming for IVF treatment at the Yamaguchi University Graduate School of Medicine to see if these findings could have real-world effects on IVF. Women who had failed to become pregnant because of poor oocyte quality after one cycle of IVF were split into two groups - 56 women were given three milligrams of melatonin before the next IVF cycle, and 59 just received a standard IVF cycle without melatonin. The team found that melatonin treatment significantly increased melatonin concentrations in the women's follicles and significantly decreased concentrations of the damaging 8-OhdG. Their results showed 50 per cent of the eggs from women who taken melatonin could be successfully fertilised, as opposed to 22.8 per cent in the control group. When the eggs were transplanted into the womb, 19 per cent (11 out of the total 56) of the women became pregnant, as opposed to 10.2 per cent (six out of total 59) in the control group. The work was published in the Journal of Pineal Research. 'This work needs to be confirmed, but we believe that melatonin treatment is likely to become a significant option for improving oocyte quality in women who cannot become pregnant because of poor oocyte quality', said Professor Tamura. 'Our next step is to analyze exactly how reactive oxygen species harm the oocyte, and how melatonin reduces oxidative stress in the oocyte'. Professor Russel Reiter from the UT Health Science Center, San Antonio, Texas, who co-authored the paper, agreed. He told BioNews: 'it is important that this work be independently confirmed on larger numbers of subjects'. But he added that the findings 'make perfect sense', as melatonin has been shown to protect many different cells and tissues from oxidative damage - the same type of damage known to occur to oocytes. [ Full Article ]
News: Strenuous exercise may affect IVF outcomes
Dr Kirsty Horsey 01 October 2006
Researchers have found that women who continue to exercise while they are trying to conceive using IVF may reduce their chances of conception. The research, published in the October issue of the journal Obstetrics & Gynecology, found that women who regularly exercised for more than four hours per week - and who had done so for one to nine years previously - were 40 per cent less likely to have successful IVF treatment than women who didn't exercise. [ Full Article ]
News: World�s first� ice baby� � 25th birthday
Geoffrey Planer 30 March 2009
It is twenty five years ago this March that the first child from a frozen embryo came into the world. Zoe Leyland was born at the Queen Victoria Medical Centre in Melbourne, Australia on 28 March 1984, helped on her way by Dr Alan Trounson and Dr Carl Wood who made medical history. The decision to try 'test tube' fertilization and embryo freezing was taken by them and Zoe's parents – mother a 33 year old New Zealander and father a 38 year old British born Australian resident. Her mother had hormonal stimulation and produced eleven eggs which were frozen using a new type of controlled rate freezer made by London company Planer plc. One of these frozen embryos became Zoe who weighed in at about 5 lbs or 2.5 kilos.
Zoe and Professor Trounson set a trend and since then, of the three million or so babies born via assisted reproduction IVF techniques, some 20% or about 600,000 are estimated to have been created from frozen embryos. The world's first 'fresh’ test tube baby was Louise Brown born in England in 1978, but Zoe came from an embryo that had been frozen for a time before being thawed and implanted. To allow cells to survive liquid nitrogen temperatures (-196°C) the embryos had to be treated with cryo-protectant, then frozen down in the Planer freezer with extreme precision using different temperature ramps before they could be stored in liquid nitrogen. This controlled rate freezing procedure was a breakthrough in 1984 but is now common and most IVF laboratories worldwide have rate freezers. Freezing an embryo allows physicians to mitigate multiple births by replacing one embryo at a time and storing others or spares for later use; it may also help in allowing a patient to 'recover hormonal equilibrium' by delaying implantation until the drugs to induce the production of multiple eggs have cleared her body. Rate frozen embryos appear to develop into equally healthy children compared with ‘fresh’ IVF ones. Recent studies from Denmark, Australia, the USA and Finland have indicated they are even healthier.
The controlled rate freezing technique, originally suggested over thirty years ago by British Scientist Professor David Pegg, enabled Planer plc to pioneer this equipment. Many thousands of units are in constant use all over the world in IVF labs, hospitals and research institutions. Controlled rate freezing is needed before storing many cells in liquid nitrogen – in areas such as cord blood banking, bone marrow transplants, botanical matter, semen, oocytes, botanical seeds, skin, ovarian tissue, heart valves and blood vessels.
Professor Alan Trounson, currently president of the California Institute of Regenerative Medicine, became a world authority on assisted reproduction and went on to pioneer work in the stem cell field. Alan Trounson is now based in San Francisco and has had a highly distinguished career in assisted reproduction, stem cell and gynaecological research in academic institutions after Monash University in Melbourne.
Recently Louise Brown, the first IVF baby, had her own child naturally – Zoe has no such plans yet and having finished her degree is working in Melbourne. [ Full Article ]
News: Frozen sperm as good as fresh
Dr. Kirsty Horsey 17 May 2004
A review of IVF procedures undertaken in the last ten years at the Mayo Clinic in Minnesota, US, has shown that it makes no difference to success rates whether frozen or fresh sperm is used. The results of the study were presented last week at the Annual Scientific Meeting of the American Urological Association in San Francisco.
The researchers reviewed 2,039 IVF cycles that took place at the clinic between 1993 and 2003. Fresh sperm was used in 1580 cycles and frozen sperm in 309 cycles. The overall outcomes of IVF using frozen and fresh sperm were compared, as well as comparative outcomes for various methods of sperm retrieval, including MESA (microsurgical epididymal sperm aspiration), TESE (testicular sperm extraction) and electrically stimulated ejaculation. The outcomes measured included the average fertilisation and pregnancy rates, embryo quality and the likelihood of having at least one live birth from a single IVF cycle. When comparing the use of fresh or frozen sperm, no difference was found in the pregnancy rate or the number of live births. The study's lead author, Dr Alan Thornhill, said that the researchers were concerned that frozen sperm might reduce the birth rate, but now, he said 'we believe that concern is unwarranted'. Dr Shane Russell, leader of the research team, told the conference that the 'data supports the continued and expanded use of frozen sperm for IVF'. Dr Thornhill added: 'IVF can be a physically, financially and emotionally draining process for couples, and use of frozen sperm eliminates the pressure of obtaining sperm on a specific day and unnecessary risk to the woman due to ovarian hyperstimulation'. [ Full Article ]
News: Louise Brown, world's first IVF baby, to have child
Dr Kirsty Horsey 11 July 2006
Louise Brown, the world's first test tube baby, is expecting her own child. Now aged 27, Louise was born after the first successful IVF treatment on 25 July 1978 - now she and her husband, Wesley Mullinder, are preparing for their first baby in January. [ Full Article ]
Announcement: Today (25th July) is World Embryologists Day
Liesl Nel-Themaat, Ph.D. 25 July 2013
Today is World Embryologists Day. A day to celebrate the scientists in reproductive medicine. This day was chosen because it is the birthday of Louise Brown, the first IVF baby. THe survey and responses for the creation of this day can be found at http://www.fertaid.com/FertAid/FertAid_Surveys.asp?SL=10 I know this might be too late, but I thought to make it fun, we should do a little theme. In honor of Steptoe and Edward's most famous moment and the infamous picture of them holding Louise in their green scrubs, I purpose we all wear something green tomorrow. If you don't have green scrubs, but in a green hair band or something. Just thought it would be fun and a great way to celebrate together. HAPPY WORLD EMBRYOLOGISTS DAY!!!
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News: A minimum age limit for IVF?
Dr. Kirsty Horsey 06 October 2005
Some UK couples seeking help to have children will have to wait until their thirties before they qualify for state-funded IVF treatment on the National Health Service (NHS), according to a report in the Independent on Sunday (IOS) newspaper. While many health authorities set an upper age limit for treatment because the likelihood of success declines with age, many fertility experts think that setting a lower age limit of 30 years or above is 'cruel'. [ Full Article ]
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days, it cannot even be said that they represent the beginning of a human life: they equally well might represent the beginning of two or more lives (Harris, 1998).
