Human Genome Research Project --- "Genes, Society and the Future: Volume I" [2007] NZLFRRp 3

	Home \| Databases \| WorldLII \| Search \| Feedback New Zealand Law Foundation Research Reports

Another twelve months, and a further public report on the significant and thoughtful work being undertaken by the New Zealand Law Foundation-sponsored Human Genome Research Project. The vision and commitment of those who inspired the project, and the dedication and scholarship of those involved, are demonstrated in the careful assessments and balanced recommendations contained in this report.

The work continues in areas which are sensitive, difficult and at times controversial. Evaluations or assessments of processes or procedures which impinge on the creation of life, or the quality of life, have the potential for discord and dissent. That is not a reason why, as a society, we should shy away from facing the challenges that are raised and improving our ability to deal with them. They are matters which have manifest consequences for individuals, their families and the wider community. They cannot be swept under the carpet.

As science stretches boundaries and offers new potentials, the way in which these approaches are utilised and exploited becomes more and more critical. At one extreme some say that you never tamper with nature, while at the other extreme some assert that there should be an uncontrolled environment in which anything that can be tried should be tried.

As with most things in life, extremes are normally unsustainable. However, striking the balance, accommodation and melding of competing interests require vigorous and objective assessment by independent thinkers.

This past year has shown that the team of researchers is well able to provide relevant input into these critical debates. The outcomes and recommendations will not be attractive to or embraced by everyone. That is the very nature of the project. The real contribution the team makes is in the presentation of unbiased, informed and intelligent assessments of the competing strands coupled with sound recommendations and with the reasons for their conclusions clearly articulated and available.

That is the very heart of mature dialogue and discourse. The report provides base information for those who will make the ultimate decisions about how we move forward together – a resource which can be turned to with confidence.

Striking evidence of the importance of this work is the exciting announcement of an endowment provided to the University of Otago for the establishment of the New Zealand Law Foundation Chair in Emerging Technologies. This new professorship and the associated Law and Policy Centre for Emerging Technologies will ensure that the work begun by the project will continue to provide research and evaluation of international significance which add value in the development of sensible alternatives in these areas which are of such importance.

The first report of the Humane Genome Research Project set the scene for an extraordinary exercise that breaks new ground in exploring issues emerging in science that have implications for all society.

The New Zealand Law Foundation is once again delighted to be the catalyst for such important research and to see the publication of the second report from the project.

This second report looks into wider applications of PGD, newborn screening, genetic testing on children and new genetic testing techniques such as microarray technology. The report also picks up on one of the early key concerns of the Foundation regarding the role of the public and consultation in decision-making. In this regard it is particularly pleasing to see a recommendation about the establishment of a Maori ethical framework for genetics.

The report issues a plea for better public understanding of the benefits that genetic testing can bring to individuals, families and communities. It appeals to general practitioners and health professionals, many of whom were trained before the discovery of the human genome, to gain more awareness and understanding so they are better placed to help parents facing difficult decisions in what can be a bewildering world of science.

This New Zealand Law Foundation initiative, with the leadership of Professor Mark Henaghan at the Otago Law Faculty, takes another vital step towards positioning the law and policy in New Zealand to meet the legal and ethical challenges arising from genomic technology. The Otago work is part of an international collaboration that draws on worldwide expertise. While the focus is on New Zealand, the findings will be far-reaching and have relevance to other legal systems.

The independence of the research remains an important aspect of the project that adds weight to the findings and recommendations.

It is important to acknowledge the efforts of the Advisory Review Committee comprising the Honourable Justice Bruce Robertson, the Honourable Justice Michael Kirby AC CMG, Professor Ingrid Winship, Professor Colin Mantell and Professor John Burrows QC. The Committee’s recommendations and assistance have been invaluable to the Law Foundation.

It is also important to acknowledge the Law Foundation Trustees for their continuing support of this project, and Director Lynda Hagen whose commitment to this project and ongoing efforts are very much appreciated.

“In applying and advancing scientific knowledge, medical practice and associated technologies, human vulnerability should be taken into account. Individuals and groups of special vulnerability should be protected and the personal integrity of such individuals respected.”

The New Zealand Law Foundation Trustees and their Executive Director, Lynda Hagen, had the vision that the emergence of genetic technologies in medicine would pose new challenges for current and future regulatory frameworks, and that thoughtful, strategic and balanced scholarly work by a team of scholars would help inform policy and the law for New Zealand both now and into the future.

That vision led to the creation of the Human Genome Research Project, Te Kaupapa Rangahau Ira Tängata: Law Ethics and Policy for the Future, based at the University of Otago and sponsored by the New Zealand Law Foundation.

The goal is to discuss options for legal, ethical and regulatory policy that will be adopted in New Zealand and internationally. Policy development and law reform need to address new knowledge and the implications resulting from advances in genetic technology that can be complex and made more challenging by a number of factors, for example: the speed of discoveries in new understandings and applications; the plurality of opinions, attitudes and perceptions; the importance for scientists and clinicians to conduct research and undertake innovations; market pressures and consumer demands coupled with an increasing degree of global connectedness; and evolving social expectations and norms.

To encourage wide-ranging analysis and reflection as much as possible, the Project has been designed to be interdisciplinary and international. In comparison with international initiatives in this area, this Project is unique in having such a full array of perspectives – all focusing on the same issues at the same time.

The Principal Investigator of the Project is Professor Mark Henaghan, Dean of the Law Faculty at the University of Otago.

The researchers for this report contribute from a range of disciplines that include:

Richman Wee, formerly of the Health Research Council of New Zealand, manages the Project.

The Project has contact with the Ministry of Health, the Advisory Committee for Assisted Reproductive Technology (ACART) and the Ethics Committee for Assisted Reproductive Technology (ECART) set up under the Human Assisted Reproductive Technology Act 2004, the National Screening Unit, the Bioethics Council, the Ministry of Justice, the Office of the Privacy Commissioner, and the Law Commission.

The direction of the Project emerged from a three-month scoping exercise that was undertaken in the summer of 2003: The Regulatory Implications of the Human Genome Project for New Zealand, Phase 1, involving Professor Mark Henaghan, Professor Donald Evans, Dr Tony Merriman, Dr Ian Morison, Bevan Tipene-Matua, James

Dann, Katie Elkin, Claire Gallop, Matthew Gillett, Mereana White, and discussions with ARC.

In 2004, Dana Wensley was funded by the New Zealand Law Foundation and prepared a report on the Acceptable Limits of Reproductive Genetics: A Discussion of Ethical Principles and Regulatory Mechanisms of Control (July 2004). The aim of the report was to identify commonly held ethical principles and legal mechanisms for control that have been developed in other jurisdictions. Dana Wensley’s report showed the dichotomy between the fundamental right of reproductive freedom and society’s interest in ensuring that technology is not used in a manner that is unacceptable or which may cause harm to society in general is not as simple as it seems. Our views about how far the right to reproductive autonomy extends are coloured by our views of how private uses of genetic technology affect society in general. The report touched on a few of the wider implications of genetic decision-making, such as the effect on the family, the parent-child relationship and the community of people with disabilities. That report was written just before New Zealand passed the Human Assisted Reproductive Technology Act 2004 (the HART Act).

In 2005, Kirsty Dobbs, a summer research scholar on the Project, produced a background paper on comparative legal approaches for preimplantation genetic diagnosis.

In 2006, the first report from the Project, Choosing Genes for Future Children, was produced after six months of a fully assembled team of researchers working together. The report critiqued and communicated a wide range of issues and concerns about PGD from a variety of perspectives.

Genes, Society and the Future is the report on work carried out by the research team for 2007. The report sets out the investigation undertaken by the Project on extensions to the current scope of permissible testing of embryos at the preimplantation stage for embryos that will have the same tissue type as an existing sibling in need of stem cell transplant. In addition, the report considers issues related to the selection of embryos carrying genetic mutations that do not, with some exceptions, manifest the disorder but may transmit the disorder to the next generation. These are more controversial uses of PGD that go beyond the issues discussed in our first report.

The report examines emerging scientific techniques, and ethical and legal issues in relation to newborn screening. The section on array Comparative Genomic Hybridisation (aCGH) technology in the area of prenatal diagnosis is written in conjunction with Professor Mildred Cho of Stanford University where such techniques are further advanced than they are here in New Zealand.

Genetic testing of children is not yet widely used in New Zealand. The report analyses in detail the positions taken overseas and makes recommendations as to when it would be appropriate to test children not able to give their own consent and as to when to test children who can give their consent. Professor Sheila McLean of Glasgow University provides her research and experience from United Kingdom to this section of the report.

The ‘Warrior Gene’ controversy which captured media headlines in New Zealand and Australia highlighted some of the potential pitfalls that can happen when whole communities are genetically tested. The report discusses an ethical framework for the testing of whole communities and focuses specifically on circumstances involving genetic research with Mäori.

All these matters can raise public concern and anxiety and it is legitimate that the public should be consulted. On matters involving assisted reproduction, the main method of consultation is through the Human Assisted Reproductive Technology Act 2004 which requires the Advisory Committee on Assisted Reproductive Technology (ACART) to consult the public. The report looks into approaches to public consultation that could be used in wider contexts.

The human genome consists of all the DNA of our species, the hereditary code of life. This newly revealed text was three billion letters long, and written in a strange and cryptographic four-letter code. Such is the amazing complexity of the information carried within each cell of the human body, that a live reading of that code at a rate of one letter per second would take thirty-one years, even if reading continued day and night.

The completion of sequencing and mapping of the human genome by Francis Collins and others has enabled Dr Parry Guilford from the University of Otago Cancer Genetics Laboratory to make a significant difference in fighting gastric cancer in an extended Mäori family or whänau with unusually high rates of this disease. Dr Guilford spent ten years working with the family. Systematic research led to the identification of mutations in the E-cadherin gene amongst family members who were highly susceptible to developing gastric cancer. One letter in a code of three billion letters was out of sequence. The particular gene is important in cell adhesion and structure and is thought to suppress cell invasion; in people with the mutation, the gene is switched off. Dr Guilford found that about 70 per cent of people with the mutation contract the disease. A relatively simple blood test was developed by the researchers and 133 people from the extended family were tested. Forty-seven were found to carry the mutation in the E-cadherin gene. Those identified with the gene were then screened by a chrome-endoscopy technique which uses coloured dyes to enhance the appearance of the cancers. So far, twenty people with very small tumours have been picked up through this screening programme. They have all had a gastrectomy and are doing well. The other members of the family who were screened were found not to have the mutation. Dr Guilford said:

... that’s very significant because right across the family everyone was carrying this fear that they were going to get the disease. Now two-thirds of them are released from any concern at all, while the others have very good care and cancers are being found at a very early stage where their chances of a complete cure are extremely high.

The research was funded by the Health Research Council of New Zealand and it shows how knowledge of the genetic make-up of a person can be very helpful in preventing the onset of disease and removing the fear of disease. Society, and particularly the health of the population, has much to gain from the proper use of genetic testing and the knowledge that has been derived from the discovery of the human genome.

Since the completion of the sequencing and mapping of the human genome in April 2003, the potential for genetic medicine to be used as a testing, diagnostic and treatment tool for multiple diseases is becoming a reality. However, because of the predictive nature of genetic diagnosis, there are fears that our future may be determined for us by scientists and medical clinicians. There is concern as to how the information that is obtained from genetic testing will be used by others. This Report analyses the current and future state of genetic medicine, the potential impacts it has on society both now and in the future, and the ethical and legal principles that must be in place to protect human vulnerability and the integrity of the individual.

This Report covers the use of genetic testing before birth, immediately after birth, on children and on whole communities. It explains new genetic tools such as whole genome screening for the benefit of clinicians who may be confronted by these technologies and the public who may wish to use the new technologies.

The primary purpose of this report is to be as accurate and accessible as possible regarding just what can and cannot be done with genetic testing technologies. The emphasis is on being as fair as possible in explaining and critiquing the issues that emerge from the use of genetic technologies. The researchers who worked on this report do not come solely from one discipline. This minimises the possibility of one particular mindset – whether it be scientific, ethical, cultural or legal – dominating the analyses and recommendations. We have all worked together and argued extensively about how to interpret our findings and present them in such a way that the public can understand what is at stake in formulating the best possible legal and regulatory frameworks for the use of genetic testing in our society.

In our first Report, we made recommendations on the use of preimplantation genetic diagnosis (PGD) in situations where there is potential for a child to be born with a serious impairment. In this Report, we look beyond that situation: first, to where PGD is used to select what have become known as ‘saviour siblings’. Put simply, ‘saviour sibling’ refers to the selection of an embryo with cells that can be used once the child is born to help treat an already existing child in the family who is ill. At present, the guidelines in New Zealand regarding selection of an embryo for this purpose are narrow. A major limitation at present is that the child who is ill must have a familial genetic disorder. Children who are suffering from an illness which is not caused by a familial gene but is the result of spontaneous mutation (for example sporadic haemophilia which is not passed down through families but causes serious illness for the child) would not have access to this procedure. Such a limitation is unjustifiable. The underlying reason for the current limitation is that there will be

some benefit to the embryo if a familial gene which could cause harm to the embryo is not selected. However, this position is unconvincing in the light of arguments as to the potential benefits of modification of the current situation. The major benefit is that a wider range of sick children, with serious or life-threatening conditions, and their families would have access to the option of a saviour sibling, for the benefit of the sick sibling and the family as a whole.

We recommend that the current limitation on the use of PGD to select a saviour sibling, which requires there to be a familial genetic disease (which means a disease that runs through the family), is too narrow. It should be possible to use PGD to conceive a child who may provide cord blood for a sick sibling who is suffering from, or has suffered from, a condition which is serious or life threatening, but is not necessarily a familial disease.

The current guideline restricts creation of a saviour sibling to situations where there are no other possibilities for treatment or where tissue is unduly difficult to obtain. The problem is that while cord blood from a public registry may contain a reasonable match for the sick child, sibling cord blood may constitute the best chance for a successful outcome. The current guideline is too onerous and inflexible. The emphasis should be on the best possible clinical outcome for the sick child rather than, as currently, on exhausting all other clinical options.

We recommend that, while other treatment possibilities and sources of tissue should be explored, if the transfer of blood tissue from a saviour sibling confers a reasonable chance of a disease-free life for the recipient sibling, that choice should be available to the family.

At present, if a saviour sibling is conceived to help an affected child, the current guideline says that the planned treatment for the affected child will utilise only the cord blood of the donor child. This limitation exists because of concern for potential exploitation of the vulnerable donor child. This guideline is beyond the authority of the Human Assisted Reproductive Technology Act (HART Act) 2004 because the Act is limited to assisted reproductive procedures and the use of sibling bone marrow for transplant which occurs after birth is not within the scope of the Act. The guideline is not consistent with current law and practice in relation to naturally conceived children whose bone marrow may be used to help a sick sibling.

We recommend removal of the guideline which says the planned treatment for the affected will utilise only the cord blood of the future sibling.

There is concern in the research literature in this area that a child brought into the world to help treat the illness of another child may be vulnerable to exploitation as a potential donor of other tissue and organs. In this argument, the child is denied

an open future and is essentially commodified. We note that the law concerning donation by children is to be found in well-established common law rules, which generally prioritise the interests of that child over the interests of third parties.

We recommend that, if there is to be ongoing donation of blood tissue or bone marrow, then it is good medical practice to require the appointment of an appropriately qualified advocate for the donor child and an independent physician to ensure the donor child is not being exploited.

We recommend strongly that the Ministry of Health set up a register to record the births of all children born to supply blood tissue to a sick sibling so that empirical studies may be undertaken on the effects on children who have been donors for their siblings.

Some people are carriers of genes that will not harm them in any way but that can be passed on to a future generation possibly leading to a serious disorder. The question we consider is whether PGD should be used to select against embryos which are carriers of a genetic disorder. An embryo that carries, but will not develop, such a disorder for the resultant child creates a 25 per cent chance that there will be an affected grandchild in the future.

Selection against carrier embryos may be justified on grounds of reproductive liberty and the reproductive and psychological interests of the future child. It can also be based on the concept of intergenerational benefit, whereby future members of the family are no longer at risk of carrying affected embryos. Arguments against allowing negative selection of carrier embryos are that it involves the destruction of healthy embryos; is an exercise based on genetic essentialism; harms society by reducing genetic diversity; and potentially stigmatises healthy carriers. Selection against carrier embryos reduces the success of a PGD cycle by reducing the number of available embryos, and has resource implications.

On a literal interpretation of the HART Order 2005, where the threshold test is ‘serious impairment’, negative selection against carrier embryos of X-linked disorders is permitted. The purposes and principles of the HART Act 2004 are broad enough to permit carrier testing and negative selection both as a contingent procedure to PGD and as the primary purpose of testing in the case of X-linked disorders.

The postulated harms of carrier testing are not sufficient to displace the presumption of reproductive liberty in this context. The greatest potential for societal harm is that prospective parents may feel they have a ‘real choice’ aside from rejecting a carrier embryo. This can be dealt with by appropriate information from the clinicians involved on a case-by-case basis, rather than outright prohibition; for example, prospective parents would have to be informed that the number of available embryos

would be reduced and that everyone carries a certain number of recessive mutations. Some individuals, for example, are in high-risk ethnic groups with regard to being a carrier for certain conditions. Carriers of cystic fibrosis are found with greater frequency among people of European descent, while carriers of sickle-cell anaemia are found with greater frequency in people of African descent.

We recommend that it should be permissible to choose to select against ‘carrier embryos’ which carry serious disorders, such as X-linked disorders like haemophilia.

The future use of PGD will be influenced by technological advances. A recent development involving preimplantation genetic haplotyping (PGH) has the potential to increase the number of single-gene disorders that may be tested for and, in the case of X-linked disorders, to increase the number of embryos available for transfer by identifying unaffected male embryos. PGH was used in the United Kingdom in 2006 by parents who were both carriers of a cystic fibrosis mutation. The couple already had twins, one of whom had cystic fibrosis. With the help of PGH, the couple had a second set of twins who were free from cystic fibrosis.

The Advisory Committee on Assisted Reproductive Technology (ACART) has a crucial role in regulating assisted reproductive technology in New Zealand. The HART Act 2004, which establishes and provides ACART with direction for its deliberations, allows for wide parameters within which the Committee can operate.

The deliberations of ACART and its engagement with the public are an integral part of its successful functioning. Given the vital role that the Committee plays in regulating assisted reproductive technology in New Zealand, particularly through the issuing of guidelines for use by the Ethics Committee on Assisted Reproductive Technology (ECART), it is important that ACART takes a considered approach with regard to its deliberations.

The HART Act 2004 requires that the Committee undergoes consultation and takes public submissions into account in the formation of guidelines. Given the flexibility of the HART Act 2004, there are strong democratic reasons in favour of involving the public in the development of ACART guidelines. It is therefore important for the Committee to establish its approach towards involvement of the public. This will assist the Committee in its functioning, and also give members of the public some insight into what they can reasonably expect from the consultation process.

The approach that ACART takes regarding the use of information arising from public consultation will depend on its overall method of deliberation. The example provided by the Environmental Research Management Authority (ERMA) shows a

thorough approach towards establishing the deliberative workings of a committee adjudicating over ethical matters. The breadth of issues that ACART must consider would favour the establishment of a less rigid and less formal approach than that of ERMA, while retaining the advantages of robustness.

The information provided through consultation can meaningfully contribute to ethical deliberation. It can provide real-world considerations that are likely to influence the effectiveness or consequences of ethical policy. It can help to reveal the range and nature of interests, and therefore the potential harms, benefits and wrongs that should be considered in reaching a decision. The reasoning of the Committee should be clear and reasonable.

We recommend that is important for ACART to demonstrate transparency of reasoning, especially in relation to the way in which a decision was reached by the Committee and why a particular decision was favoured over others that were also considered.

Currently, in New Zealand, children at birth have their heel pricked to test for metabolic conditions which, if found early enough, can be treated. The present New Zealand newborn metabolic screening programme is a competent and successfully run programme with good detection and participation rates. The programme staff is committed to the success of newborn screening, is progressive in attitude towards the benefits of screening and fosters good links with other international programmes. The programme has avoided negative publicity, and has carefully managed access to the Guthrie cards in the interests of maintaining public confidence. New Zealand is well placed to have a flexible and responsive screening programme, given the small population; the single medical contact for each child (the lead maternity carer); a nationally consistent screening panel; centralised testing; and public funding.

New Zealand is following international trends in newborn screening but not in too hurried a fashion. Even before expansion, the New Zealand programme was screening for a respectable number of serious disorders (more than, for example, the United Kingdom). New Zealand has been able to use the implementation lag to absorb knowledge about and experience of these new technologies from overseas, and to put in place adequate support services, such as the employment of a clinical metabolic specialist, before launching tandem mass spectrometry (MSMS) screening.

There is little public awareness of the successful New Zealand newborn programme, beyond recognition that the ‘heel prick test’ is a routine procedure for newborns. The National Metabolic Screening Programme has been consulting on various aspects of the programme and the storage and use of the Guthrie cards. This consultation is a

positive move given the anecdotal evidence of growing anxiety surrounding the use of DNA samples and Guthrie cards. A small but growing number of parents who are requesting the return of the cards points to concern about potential uses of the DNA samples. This concern may have implications for the screening programme in the future.

We recommend that more public education and information regarding the programme, particularly in antenatal classes and on the internet, be made available to the general population.

Publications, whether scientific or popular, about newborn screening should be made more widely available to parents and members of the public who are seeking more information than is currently contained in educational pamphlets.

We recommend that audit, epidemiological and cost-effectiveness data should be gathered from the programme.

Given the constrained levels of financial support, and small number of key staff, this research would best be done in association with other researchers.

Screening expansion is an exciting move for many and the programme expects that an additional five to ten children with genetic disorders will be detected through the programme per annum. The MSMS screening is also to be used as a metabolic diagnostic tool. Given the expansion of newborn screening, and the versatility of the new technology and its potential for disease prevention, the purchase of MSMS was perhaps worthy of better governmental support, rather than the programme’s reliance on a children’s charity for financial support.

The newborn metabolic screening programme can be classed as a genetic service. At present, there is unofficial and ad hoc national co-ordination with respect to genetic services. There is apparently a review underway of the 2003 National Health Committee (NHC) report on co-ordination of genetic testing in New Zealand by the New Zealand District Health Boards, presumably with a view to implementation of at least some of the report; there is no other information available on this review at present. Newborn metabolic screening should be acknowledged in future genetic co- ordination initiatives; though, equally, the programme legitimately belongs within the mandate of screening services.

We recommend that when scientifically accurate, clinically useful, cost-effective, high-throughput screening processes are available, the pros and cons of inclusion of early onset, untreatable disorders, such as lysosomal or peroxisomal storage disorders, should be publicly discussed.

If screening of untreatable disorders is introduced, then there must be improved education so that parents are aware of the implications of screening.

In the future, it is likely that DNA screening for individual disorders will be introduced as adjunct tests to the metabolic screening programme. In view of the speed at which science is developing in genetics, it is impossible to say, with any certainty, what the longer-term future holds for newborn screening or even whether the screening time point might move to (non-invasive?) antenatal screening. Whole genome sequencing remains likely in the future, although how and when this information might be used, after the initial sequencing process, remains to be seen.

Expansion of newborn screening into DNA screening will require more characterisation of minority populations in New Zealand. It is likely that there will be differing allele frequencies for various disorders in these populations, compared with populations of Northern European descent (as for cystic fibrosis in the United States). It is also possible that a small number of genetic disorders, rarely found in Northern European populations, are more commonly found in minority populations here. If any were identified, there would be merit in evaluating them for screening.

We recommend that the current Wilson-Jungner criteria, which have been used as a foundation for newborn screening and which were originally formulated in 1968 for chronic adult disorders, need to be reformulated for newborn screening.

Parents should be informed about screening of newborns in terms of their rights under the Code of Rights and the uses to which newborn blood samples will be put. The analysis in this part of the Report is grounded in the rights-based Code of Rights, and takes into account the public health paradigm and how genetic risks are dealt with in families. It is important to distinguish public health screening from personal clinical services. Traditionally, public health law was prescriptive and compelled participation. This is in contrast with the present consumer-based approach which actively promotes informed choice and consent, and which seems more in keeping with the complexities and sensitivities surrounding genetic medicine.

We recommend that information about newborn screening should be given to parents by or during the third trimester, and again before samples are taken from the newborn. Parents should be informed about the entire screening pathway and what might occur before they take the first step in participating in the newborn screening programme. We recommend that clear, unambiguous information be given to parents, emphasising that the purpose of participation in the screening programme is in the interests of the newborn.

We recommend that parents or guardians be kept informed throughout the screening process, including being notified about the results.

The policy of ‘no news is good news’ may have to be reconsidered in the light of complex issues raised by technologies that reveal carrier status and the question of whether screening should be extended to include late-onset disorders.

Activities to monitor and evaluate the programme need to be more explicitly stated in information given to parents. Related to this is the importance of distinguishing between initiatives taken for the purposes of fulfilling the aims of the programme, such as picking up early metabolic conditions and monitoring the programme, and those that go beyond the aims of the programme, such as use for general research, paternity testing and police investigations.

We recommend that policies regarding retention and use of samples should clearly make that distinction and should be explicitly communicated to the public and in particular to parents.

The degree and scope of information that can be derived from dried blood spots with the use of new and emerging DNA technologies will potentially be very significant and have far-reaching implications. There is tremendous long-term value in retention, for example, for the purposes of quality management, programme expansion, research on testing, and treatment and epidemiological studies. Current and relevant scientific literature on the stability of metabolites, DNA extraction and testing technology and optimal storage conditions needs to be taken into account with regard to any policy development in this area.

We set out two options for reconciling the inter-relationships between the various provisions of the Code of Rights on consent, storage and quality assurance and the National Health Committee (NHC) screening guidance. The first option involves more actively communicating information about clause 7(9) and clause 7(10) of the Code of Rights.

Clause 7(9) provides the right to the return or disposal of blood samples taken in the course of a health-care procedure and clause 7(10) involves an exemption to the requirement to obtain informed consent for quality assurance (QA) activities such as professionally recognised QA programmes, external audits of services or external evaluations of services. The second option involves explicitly prescribing, with legal authority, a minimum retention period to guarantee all samples are available for quality assurance-related activities.

We recommend that policies and procedures setting out, for example, the taking and documenting of informed consent be publicly communicated and made more widely available to help increase parental and public awareness, understanding and confidence.

new PossiBilities For newBorn genetic screening: screening For genetic suscePtiBility to common Disease

Many challenges have been identified since the completion of the Human Genome Project, with one of the most significant, perhaps, being how genetic susceptibility testing (or genomic profiling) might be integrated into medical practices such as newborn screening.

The review of the psychosocial effects of newborn genetic susceptibility testing has highlighted the fact that there are several good reasons to be concerned about such testing. These include features inherent in the newborn period; characteristics of the tests themselves; and evidence from previous and current newborn screening programmes. There remains a relative paucity of empirical research in this area but evidence, including the results of research for this Report, is gradually accruing to suggest that families generally cope well with type 1 diabetes (T1D) genetic risk information concerning their children, if it is conveyed sensitively. At this stage, the research remains fairly limited both in focus and duration and the need for further research in this area has been highlighted.

Screening children for susceptibility to certain diseases which have a genetic base, for example T1D, has the potential to enable parents to ensure that the environment is appropriate for a child with the susceptibility. The major concern about widespread uses of such screening is that parents may overreact if they find out the child has a susceptibility to diabetes and overprotect the child.

In this Report, we have carried out our own research to see what the likely consequences would be. We studied three mother-baby cohorts: thirty-eight infants at increased genetic risk of T1D, seventy-three at low genetic risk and seventy-six who had not undergone testing. Our main focus was to see whether or not the parents who knew of the risk would have an urge to overprotect their child and to be overly zealous about surveillance. In fact, the outcome was surprising. The group of parents who knew their child had an increased risk of T1D were in fact lowest on the anxiety scale in terms of how they related to their child. This is only preliminary research but it does show that information about a child’s risks does not necessarily lead to parents becoming over-anxious. There is potential for such information to empower parents to ensure that the environment is healthy for the particular child.

Achieving a proper balance between the social good that may come from performing this type of research involving children, and the level of protection offered to child participants, is a significant challenge. Such research itself involves complex ethical and social issues.

We recommend that particular attention must be given to minimising risks to children and implementing procedures for obtaining the informed consent or assent of parents and child participants when screening newborns for genetic susceptibility for common diseases.

Empirical research concerning the potential psychosocial harms of newborn susceptibility testing is essential if we are to make rational decisions regarding the use of such tests. Analysis of harms and benefits is fundamental to the consideration of the introduction of new screening programmes.

Newborn screening for genetic susceptibility is currently only available in research settings because of the lack of detailed knowledge concerning harms and benefits; the lack of preventative measures; and the relative expense and complexity of testing. The research carried out here aims to provide more information on which to base decisions about future uses for these tests.

If the pathogenesis of T1D is eventually better understood, and a preventative measure developed, even if only partially effective, then the benefits of screening may well outweigh the risks. If this eventuates, screening for genetic susceptibility to T1D should be reassessed using the usual processes and screening criteria applied when considering the introduction of a new test on standard newborn screening panels.

Genetic testing raises new issues from those involved in other medical contexts, particularly for children. Most of the concerns relevant to minors are prompted by the familial and predictive aspects of genetic information. Genetic testing may have far greater personal implications for other family members than inquiries made in other medical contexts, and has the power to be more predictive of future health, which has implications for the minor’s best interests and autonomy. Genetic information can also be difficult to understand and its implications are easily misunderstood, particularly in respect of its predictive power or lack thereof.

As genetic testing increasingly becomes part of regular practice, and is more widely available, it seems likely that parents will want to test their children. In our analysis, we looked at both children who are too young to give consent to the testing themselves and those who have sufficient understanding to give their own consent. With regard to very young children, there is a wide range of policy guidelines and some empirical research weighing up the risks and harms of testing, which all suggest that it is both ethically and legally responsible for parents to test children for conditions for which, if detected at an early stage, the environment can be adapted in order to give the child the best opportunity of coping with the disease. It is also generally accepted that, if

early testing would enable treatment or cure of the disease, then the testing should be undertaken – again to give the child the best possible chance of survival.

The main controversy arises in relation to diseases which have a late onset and diseases for which there is no effective cure, such as Huntington disease. In such cases, once a person has the genetic markers, the disease will inevitably arise at some stage, barring death from unrelated reasons. Child rights advocates argue that these decisions, because there is no immediate benefit to the young children, should be left to the children once they have sufficient understanding to make their own choices. The emphasis is on the children exercising their own autonomy rather than decisions being taken for them before they have had a chance to decide whether they wish to know about their future health status.

There are two strong objections to this point of view. One of them is that we allow parents to make lots of decisions for young children in terms of what they eat and how long they stay up at night and, above a minimum threshold, what sort of conditions they live in. All of these things have the potential to harm the future autonomy of the child and may not necessarily be in the best interests of the child but they are the price we pay in order to give parents a sufficient degree of freedom to bring up children as they see fit. On this line of reasoning, testing a child at a young age for a condition for which there is no treatment is just another parental choice, which may or may not harm the child in the future. The choice should be for the parents, because there is no overwhelming evidence that the child would be harmed by such early testing. The other objection is that within families knowledge about diseases at an early stage is inevitable to some degree because of family histories, even without genetic testing having been carried out. The testing simply confirms suspicions that are already present. If, for example, another member of the family has had Huntington disease, there is a reasonably strong chance that a future child in that family group could also have that disease. Whether or not the family’s genetic understanding is sufficiently sophisticated is another matter; and, of course, the symptoms of Huntington disease may not have been identified as such.

A recent poll published by the University of Michigan’s CS Mott Children’s Hospital claims that 54 per cent of the 1500 people who responded to the poll (out of a total of just over 2000 questioned) thought that genetic testing for disease risk was worthwhile even in the absence of treatment, while 30 per cent would want genetic testing for themselves or their children only if an effective treatment were available.

A recent 2007 meeting jointly sponsored by the Clinical Genetics Society and the British Medical Association concluded that, in the absence of childhood onset or the availability of medical interventions, predictive testing for adult-onset disorders should not be offered; nor should carrier testing, where the aim of the test is purely

to promote the child’s reproductive choice. The results of the meeting showed that clinicians generally seemed more sympathetic to respecting a child’s future autonomous choice and preferred to delay testing wherever possible. There were significant differences between European countries, with Southern and Eastern European countries being more likely to carry out carrier testing at the request of a parent than Northern or Western European countries.

The United Kingdom, possibly because of the Gillick case which recognised that children should be able to give their own consent once they understood the issues involved, tends to test minors two years earlier than Germany or France. The meeting agreed that imposing a strict age limit for genetic testing is generally inappropriate. The meeting concluded that, despite calls in 1994 for prospective and retrospective psychosocial research on genetic testing of children, evidence remains sketchy and more research is urgently needed. The 1994 guidance identified genetic testing of children undergoing adoption as a potential ‘special case’ for testing. It was generally felt that special cases for adoption were less justifiable than they had been in the 1990s.

Professional guidelines on genetic testing of minors take a generally prohibitive stance towards genetic testing of minors who cannot give their own informed consent for untreatable late-onset disorders. Medical benefits comprise the main justification for any genetic testing of children, although special circumstances, in which testing may result in greater psychosocial benefits than harms, are considered. There is some ambiguity regarding testing for untreatable early-onset conditions. There is less consensus regarding carrier testing of minors and fewer recommendations – those that exist take a more lenient view of such testing than testing for untreatable late- onset disorders.

Many of the professional guidelines, including those applicable to New Zealand practitioners (the HGSA Policy on Predictive Testing in Children and Adolescents), provide that minors can make their own decisions about genetic testing provided that they meet varying standards of competence, understanding and voluntariness.

There is a variety of evidence regarding the attitudes, awareness and practice of different groups of health professionals towards genetic testing of children, despite guidance against testing children for untreatable late-onset conditions. Geneticists appear more reluctant to test minors, particularly where there are no medical benefits, than are other physicians, parents and the general public. Geneticists, other health professionals, students, parents and the public give similar reasons regarding the appropriateness of genetic testing of minors for non-medical reasons, most of which accord with the issues considered in the professional guidelines. Reasons offered in favour of testing include parental desire to know; parental autonomy; opportunity

for planning; resolution of uncertainty for young people; relieving of anxiety; and reproductive decisions. Arguments given against testing include protecting the minor’s autonomy; lack of medical benefit; possibility of harm; privacy concerns; and concerns over stigma. There appears to be more willingness to provide carrier testing of minors than predictive testing.

There is evidence that health professionals involved in genetics, paediatrics, neurology, haemoglobinopathies and other areas of medicine are approached about the possibility of genetic testing of minors, and that many health professionals and laboratories are acceding to requests, and performing genetic tests on minors. While most tests are undertaken for medical reasons, a significant number of tests have also been performed for non-medical reasons.

There is very little evidence available regarding attitudes towards, and the practice of, predictive or carrier testing of minors in New Zealand. At this time, requests for predictive or carrier testing of minors are very rare, and testing currently proceeds on a case-by-case basis.

While there is some professional guidance on genetic testing of minors from the HGSA, and laboratory protocols on predictive testing generally, these do not appear to be well publicised or formalised. The lack of a formal structure and process for genetic testing requests also means that GPs and other health professionals may be making inappropriate requests for testing that are not actioned by pathologists, resulting in a waste of time and resources, and increased stress for at-risk families and children.

It is vital that GPs and other health professionals know more about genetic testing and genetics services in New Zealand, so that they can better facilitate informed consent; recognise and acknowledge any limitations in their expertise, particularly as they will influence their patients when discussing testing possibilities; know when to refer patients for genetic testing; and can offer some degree of genetic counselling, if required.

Empirical evidence as to the benefits and harms of genetic testing is very limited. However, the most recent and extensive evidence points towards testing having the potential to be more beneficial than harmful for competent minors who request it. For some of the purported benefits and harms there is no evidence, or only inadequate evidence. Other purported harms do not sufficiently justify a decision against genetic testing of competent minors upon request because they relate equally to other health- care contexts; relate to adults also; or can be mitigated or resolved via alternative methods, rather than blanket prohibition. Many of the potential harms would not be an issue if correct procedures were adhered to, particularly around clear protocols and timeframes for counselling and testing and clear rules and procedures regarding method, timing and persons to whom disclosure of results will be made.

The same limited body of evidence exists against which to judge the effects of genetic testing of minors who cannot give their own consent. However, different conclusions have been reached because of the different consequences of testing each group. When testing a child who cannot give consent is not clinically indicated, there is reason to suspect that psychological or social harms may arise from such testing: whether from early knowledge that one will inherit an untreatable disorder because one has had no say in whether to be tested; because parents may treat the child differently; or because of an inability to prevent parental dissemination of one’s genetic information.

We recommend that genetic testing of children who lack capacity to consent to genetic testing for non-medical reasons should be treated with caution. Many adults choose not to discover their own genetic risk status and the threat to the child’s autonomy and right to confidentiality are the reasons for this caution. Also, where there is a lack of evidence about what the test results may signify for the child’s health, this uncertainty is best dealt with by waiting until the child is able to make personal choices.

Predictive genetic testing for an early-onset condition for which no beneficial medical interventions exist raises fewer concerns. The same potential benefits exist but not the same harms, because the danger to the minor’s future autonomy and potential to exercise the right to not know the information is not as salient: the child may never reach an age to decide whether to have predictive testing for the disorder (having already developed it, or having passed the likely age of onset, unaffected). Thus, the putative benefits of such testing (relieving anxiety, preparing for onset, etc.) may be weighted more heavily in this context regardless of whether or not the disorder is treatable. However, given that there are no clinical benefits to such testing, and that there may be some harms (changed parental expectations and treatment of child, etc.), parental requests for such testing should still be treated cautiously.

Health professionals generally cannot inform a minor about a heritable condition in the family without the permission of the person from whom the health information was gleaned (particularly without an explicit request for the information). And yet guardians are under no legal duty to inform children of heritable conditions for which they may be at risk. Guardians can be advised by a health professional about an appropriate age and the manner in which to inform children but families will make these decisions for themselves. The available evidence suggests that parents tend to be in favour of informing their children of their genetic risks, and of informing them themselves, rather than via a health professional. It is, however, obviously a delicate and often difficult task, and the ages at which parents consider disclosure appropriate vary.

As with disclosing familial genetic risk, there currently exists no legal duty to warn minors of their genetic test results, and minors might be refused access to their test results if the information were considered prejudicial to their interests, or their physical or mental health. Deciding whether to disclose a minor’s genetic test result requires a careful, case-by-case approach. Parents do not appear to be legally obliged to inform their children of their own genetic test results. Genetic counselling will be necessary if minors are to be told that they carry a genetic mutation, and may be necessary regardless of the test result. The concerns raised by disclosure of the information, coupled with those raised by refusing to disclose the information, support our argument that carrier or predictive genetic testing that is not clinically indicated should generally be restricted to those who competently request it, and generally not be permitted on the basis of parental consent alone.

A register should be established to facilitate disclosure to persons who have reached the age of sixteen or eighteen years (or earlier if they are competent and personally seek access to the information) of the fact that they underwent genetic testing as children. Initially, the minors may be informed either that they underwent predictive or carrier testing as children, or that some information is available about genetic risk status should they wish to access it.

Such a register is the appropriate method for ensuring that people who undergo testing as children are informed of the fact for the following reasons. First, it would encourage parents and health professionals to disclose test results to children – as the fact of testing will be disclosed to them anyway. Secondly, it gives the person tested a choice regarding whether or not to access the information (assuming that he or she has not already been told). Thirdly, it avoids the difficulties of imposing a new disclosure duty that may have unwieldy and undesirable consequences in terms of monitoring, enforcement and sanctions.

Genetic counselling would be required to assist minors in deciding whether to access their test results, and to support them whatever their choice. The privacy of the register and its information must be strictly maintained.

Parents will usually be aware of their children’s results and can treat that information as their own for the purposes of disclosure. Health professionals are bound by confidentiality duties to the child and may not disclose the results except to those entitled to receive them (usually the guardians) or pursuant to applicable statutory or regulatory exceptions.

The child’s privacy interests need to be weighed against the interests served by allowing parents to disclose their child’s genetic test results to certain people or agencies, for example to school or caregivers (so that they can be alert for early symptoms, etc.), and against the parents’ rights to freedom of expression under section 14 of the New Zealand Bill of Rights Act 1990.

Competent minors who have had genetic testing on the basis of their own informed consent are entitled to the same rigorous protection of their privacy and confidentiality as are adults. This is particularly important in genetic testing because of the greater family interest in the information, and the current lack of any legal duty on parents or others to keep such information private.

Community GenetiCs:With PartiCular emPhasis on establishinG a mÄori ethiCal FrameWork For GenetiC researCh With mÄori

Genetic testing of whole communities is a way of picking up disease trends within that community. The diseases will not necessarily be genetically based. They will also be influenced by environmental factors. However, long-term studies hold out the hope that patterns of living combined with the genetic markers could lead to medical break-throughs to improve the health of whole communities. The major question here is whether, once a whole community gives up the genetic material for study and analysis, they lose control over the information in that material and whether they may be harmed by the ways in which the outcomes of the research are interpreted or released. We all remember the ‘warrior gene’ news headline in New Zealand when it was suggested that a certain gene that was prevalent in Mäori predisposed people to act more violently and aggressively. This had potential to deter people from wanting to release their genetic material for study. In this Report, we set out an ethical protocol so that communities are aware of how their genetic material will be used in research and are consulted about the release of the research findings before they are made public.

Indigenous communities have unique concerns in relation to genetic research. The impact of genetic information on them as communities is potentially greater than the impact on other, less defined, groups. Greater assurance needs to be given that the research will be conducted in accordance with robust ethical guidelines and that it will meet their expectations. Any research relationship must respect indigenous cultural beliefs and be in keeping with their values.

We recommend that researchers explain to the community what the research is about and the potential likely findings, and how they would be released, so that the particular community can make a choice as to whether or not to be involved. Genetic samples should be considered to be ‘on loan’ to the researchers for the specific purposes for which consent was obtained. Guidelines for ethics committees in New Zealand require researchers to take steps to minimise potential harm to participants. The best way to achieve this is to work in partnership with participants to ensure that they fully understand what is happening and the researcher fully understands the participants and their potential concerns.

In New Zealand, any research on Mäori health burdens should take steps to minimise harm to Mäori arising out of the research. Researchers are required to minimise harms, which generally fall into four categories: physical; psychological; social; and economic. For research involving Mäori, researchers are additionally obliged under the current Operational Standard for Ethics Committees to minimise harms that may occur to the whänau (family or community), hinengaro (emotional well- being and state of mind), wairua (spirit) and tinana (the body or physical self). The concept of harm is broad enough to include ‘pain, stress, fatigue, emotional distress, embarrassment, cultural dissonance and exploitation’.

The guidance proposes that minimisation of harm be achieved through inclusion of Mäori as ‘partners and participants in the design, implementation, management, and analysis of research about Mäori or Mäori health’. Any research on Mäori conducted in New Zealand should be based on the principles of partnership, participation and protection.

Partnership involves working with iwi, hapü, whänau and Mäori communities to ensure Mäori individual and collective rights are respected and protected. Participation involves including Mäori in the design, governance, management, implementation and analysis of research. Protection involves actively protecting Mäori individual and collective rights; Mäori data; and Mäori culture, cultural concepts, values, norms, practices and language in the research process.

The guidance describes consultation as the ‘key component’ in developing research on a Mäori health issue and is a ‘dynamic and flexible process’ involving a ‘two way communication process for presenting and receiving information before final decisions are made, in order to influence those decisions’.

The guidance calls for Mäori participation ‘in the governance and management of research’, particularly research focusing on Mäori health, and for researchers to ensure that Mäori participants have ‘the same protection as all other participants in research,

with particular acknowledgement of cultural diversity for Mäori’. The guidance specifically states that this is to include ‘protection of individual and collective rights and ownership of data as well as protection from harm’. Researchers are obliged to ‘support’ and ‘protect’ Mäori culture, language, cultural beliefs, practices, values and norms. Importantly in the context of genetic research, ethics committees are asked to consider whether mechanisms are in place ‘to ensure the Mäori individuals and groups are not marginalised in the research process or by the presentation of the research results’.

This Report responds to trends around research on genetic variation and the potential for such research to reveal information linking genetic variation to common diseases amongst Mäori. The focus is on what has been referred to as the ‘new genetics’, or the expanding nature of research on genetic variation that analyses the genetic links to common diseases, for example cancer and diabetes, as opposed to single-gene disorders and genetic diseases such as Huntington disease. ‘New genetics’ is a phrase developed to emphasise the expanding role and rapid development of genetics. Shickle defines it as ‘applications resulting from development in techniques for locating genes, their products and functions’. The key for this Report about the term ‘new genetics’ is that it is specifically about studying and identifying the genetics of more common diseases (and is not just a study of rare diseases). It involves the possibility of much more rapid and large-scale analysis of factors contributing to diseases that Mäori and other indigenous peoples suffer disproportionately.

This part of the Report explores the broader context of Mäori health by discussing Hauora Mäori frameworks and knowledge systems for addressing health disparities and contrasts these with the philosophical and scientific ideals driving ‘new genetics’. As links between genetic variation and the health of certain populations, particularly indigenous and ethnic populations, continue to be made the issues that arise are primarily driven by ethical, cultural, social and political influences. This research involved analysing the relationships between potential health benefits from genetic testing of newborns and any cultural, spiritual or ethical issues this testing may raise. It looked at the tensions between Mäori collective tribal responsibilities and individual rights with regard to the access to and use of human genetic material. This Report proposes that genetic testing research could have significant benefits for Mäori and other communities particularly if a broad approach to establishing and implementing moral, ethical and spiritual frameworks to drive such research is adopted.

This part of the Report introduces the Mana Protocols for genetic research and outlines how such protocols could be developed and used to assist Mäori (whänau, hapü and iwi), researchers, funders and regulators of genetic research.

We recommend that a Mäori ethical framework for genetics, to be administered by a Mäori ethics committee or similar body, should be established. While legitimate concerns have been raised about the genetic testing of ethnic and indigenous communities, equally strong sentiments have been expressed warning that we should be careful ‘not to throw the baby out with the bath water’. The key is to ensure that the approach to genetic research is balanced in terms of its risks and benefits, and that we do not give genetics a more negative or positive spin than is justified. The need for honesty is paramount. There are many talented and committed Mäori and non-Mäori genetic researchers who believe their science can make a significant contribution to the improvement of community well-being. If genetic research is to be conducted with kaupapa wairua Mäori as its foundation, the benefits will be significantly enhanced.

The use of microarrays allows many genetic tests to be done simultaneously on one genetic sample and changes (mutations) to be found that are currently not detected. Microarrays are being used predominantly in the research sector. There has been some movement into the clinical testing and diagnostics arena internationally, but its eventual utility in clinical screening remains to be seen. The diagnostic aspect of microarrays has been enthusiastically reported in the clinical and scientific literature and remains one of the most likely uses of the technology as the cost comes down.

There is still a technology block regarding the use of microarrays with PGD for aneuploidy screening in the form of whole genome amplification. If this problem can be overcome, microarrays could conceivably make a positive difference to implantation rates and reduce miscarriage rates for those who choose to use PGD for this purpose. PGD requires, however, that in vitro fertilisation (IVF) be used to generate embryos for testing. It is therefore unlikely that it will ever be used outside fertility clinics and, even then, only for a subset of clients. Future use remains debatable.

As the cost comes down, microarrray technologies will likely supersede the existing cytogenetic technologies as a first-line prenatal test. Arrays are faster and potentially offer more detailed screening for disorder-causing chromosomal changes. This does not preclude simultaneous karyotyping as a method of confirming any larger abnormalities, or the use of other techniques for later confirmation of an abnormal result. All cytogenetic results should be confirmed, preferably by using another method. As knowledge increases regarding the effects of medium to large chromosomal changes, (ironically) through increased testing as well as new research data, uncertainty about the seriousness of particular changes will be reduced.

There remains, however, the difficulty of explaining the technology and results to a lay audience. A number of other ethical issues have been raised around the use of microarrays for prenatal screening. In addition, microarray use in prenatal screening currently requires an invasive procedure to obtain fetal material for testing. Again, unless there are developments in non-invasive testing, this technology will be limited to those women already undergoing amniocentesis or chorionic villus sampling.

A debate is underway regarding how much genetic information is useful and the advantages and disadvantages of selective versus whole genome screening. There is a corollary with the use of whole-body CAT and MRI scans for simple health ‘check-ups’. Abnormalities may be detected that have no effect on the quality of life but, because they have been found, they are investigated or treated unnecessarily. The more targeted the microarrays to specific clinical questions, the less likely this is to occur.

Genetic services in New Zealand are currently stretched. Introduction of the routine use of microarrays would require a substantial investment, not only in technology and laboratory staffing, but also in clinical genetics and counselling personnel.

Implementation of new testing technologies in New Zealand currently appears to be driven by the clinical testing laboratories, on a cost recovery basis. There appears to be no national strategy for monitoring and introducing new techniques and technologies. While this is not necessarily a negative, it may preclude a national push for the introduction of new genetic testing tools; particularly if this were to be based in a single laboratory in competition with others. In addition, private genetic testing services have not been established in New Zealand or Australia. This may or may not affect whether laboratories offer new services. The promised follow-up to the 2003 report by DHBNZ on molecular genetic testing in New Zealand is said to be underway. We await the report with some anticipation.

Beyond microarray technologies, rapid whole genome sequencing is being touted as the next revolution in genetic testing. It is likely that rapid whole genome sequencing will become viable in the medium to long term. This technology reveals the ultimate genetic information – the exact sequence of the genomic DNA. This information is superior to the limited data from microarrays, although it is likely to need more interpretation. It is unlikely, however, to detect ploidy changes, such as trisomies, without additional analysis. Detection of chromosomal copy number variation (CNV) is the principal driver of most current and future PGD, prenatal and diagnostic testing.

Array comparative genomic hybridisation (aCGH) represents a major advance in the field of cytogenetics and offers tremendous promise in prenatal diagnosis for the detection of genetic alterations leading to serious genetic conditions. This technology, also sometimes known as molecular karyotyping, can detect differences in DNA

copy number at hundreds or thousands of points in the genome simultaneously. This technology promises to replace standard karyotyping, which uses standard microscopy to view chromosomes directly in order to detect structural variations that lead to conditions such as Down syndrome (which can be caused by trisomy 21, that is three copies of chromosome 21 instead of two, or a joining of chromosomes 21 and

14) or Turner syndrome (loss of one copy or part of one copy of the X chromosome in girls), or genetic duplications, deletions, insertions or translocations (some of which can be associated with hereditary diseases or cancers). Compared to standard karyotyping, aCGH can detect genetic variations at a much higher resolution.

Array comparative genomic hybridisation was initially studied and utilised in cancer genetics to determine how chromosome structure and function contributed to tumour development. Although it is still used for this purpose, it is hoped that aCGH will be valuable in other clinical contexts, including prenatal screening and diagnosis. In research, aCGH has demonstrated an unparalleled ability to perform comprehensive, high-resolution scans of both the whole genome and specific chromosomal regions. Physicians are looking to aCGH to increase their ability to detect clinically significant genetic alterations. Although it is already a powerful research tool, the technology is still in its early stages and has not fully transitioned to clinical use. However, in the United States, aCGH is already being offered as a clinical test in postnatal and prenatal settings. More research is necessary to determine how and in what capacity aCGH technology can and should be used for clinical prenatal screening or diagnosis. A necessary aspect of this development is a thorough consideration of the ethical implications of the new technology; this will come to the forefront as clinical use of aCGH increases.

At this stage of the development of aCGH technology, a number of recommendations can be made for clinical use. These recommendations should be revisited as information about its clinical validity and utility is obtained, and as the accuracy, resolution and cost of aCGH-based tests evolve.

First, aCGH should be used for prenatal testing only under research protocols where other data necessary for learning how to interpret aCGH data are also collected.

This information might include the results of other prenatal screening tests (such as nuchal translucency and multiple-marker blood tests) and clinical data on parents. The aCGH data should be validated by and compared to data from some other method such as standard karyotyping, FISH and QF-PCR.

Secondly, before clinical use as a prenatal test, aCGH should be used and evaluated under conditions that allow assessment of the clinical significance of the results (i.e., where phenotype and clinical information about the patient are available from newborns, children or adults).

Given the large amount of copy-number variation in the general population, even among apparently healthy people, the finding of copy-number variants may in itself be of unclear clinical significance. In the prenatal setting, very little clinical information can be obtained to aid in the interpretation of aCGH results, and it is thus not the optimal setting in which first to bring the technology to clinical use.

Thirdly, laboratories beginning to use aCGH should adopt uniform and transparent technical standards, including standards regarding what constitutes the ‘normal’ control samples with which patient samples are compared.

Fourthly, research and clinical laboratories using aCGH should anticipate the possibility of uncovering ‘incidental’ findings and make plans for handling them.

For example, if parental samples are tested, in order to interpret the findings from a fetal sample tested to detect trisomy 21, the laboratory should make advance plans for whether and how to report unexpected findings of major clinical significance that arise in the parental samples. Laboratories should also decide whether any results will be withheld.

Fifthly, informed consent to aCGH in research or clinical settings should include provision for how research subjects or patients want to handle‘incidental’ findings, the possibility of unwanted results and results of unknown clinical significance.

The diagnostic power of aCGH technology offers an exciting and revolutionary approach to prenatal diagnosis, providing a much more fine-tuned tool for genetic analysis than other currently available technologies. The detection capability, as a result of increased resolution, the comprehensive nature of the tests and the potential for faster reporting times, makes aCGH a promising new technique. However, despite the documented successes of this technology so far, more research is needed to understand its scope fully so that aCGH can be implemented as a clinical tool in prenatal diagnosis. Because the technique has not yet transitioned to clinical use, there are as yet no established standards for its application. To be sure, ethical difficulties and ambiguities will attend its clinical use. Research will no doubt continue to improve the technology; but it is also important that the ethical, legal and social implications are given serious consideration as aCGH transitions to clinical use.

The main finding which comes through in all aspects of this Report is the current lack of awareness and understanding of the benefits that genetic testing can bring to the health of individuals, families and communities. This lack of understanding and awareness is not simply within the general population but also among the medical profession, because many doctors were trained before the discovery of the human genome. Discovery of the human genome raises a whole new and different way of looking at the current and future health of individuals and communities. While genetic testing technologies are still emerging, their potential to provide information which will help people understand their health status in a better light is clear. The information that is obtained as a result of genetic testing has the potential to be misused or misunderstood. However, that is true of any information and should not be cited as a reason to deter us as a society from obtaining the information and subjecting it to careful analysis.

The full impact of the discovery of the human genome has not yet fulfilled the potential promise to help us understand the genetic structure of all diseases because the nature of disease and the interaction of genetics with the environment is complex. For the advancement of society, we must continue to explore the full potential of the meaning of our genetic make-up with an open mind. Throughout this Report, we provide legal and ethical frameworks to ensure that the potential for misuse of genetic information is avoided as much as possible. Overall, the benefits of genetic testing for the health of individuals and populations outweigh the potential harms and we hope that the frameworks in this Report will minimise the impact of those harms.

3.4.3		Clause 7.2		65
		3.4.3.1 Summary		66
3.4.4		Clause 7.3		66
		3.4.4.1 Altruistic sibling donation of bone marrow by incompetent minors on the basis of parental
		(proxy) consent		67
		3.4.4.1.1 Introduction		67
		3.4.4.1.2 Physical and psychological risks
		associated with sibling bone marrow
		donation by incompetent minors		71
		3.4.4.1.3 Justification for parental (proxy)
		consent to altruistic sibling bone
		marrow donation by incompetent
		minors		72
		3.4.4.1.4 Neonates as donors of bone marrow –
		Is there a distinction?		74
		3.4.4.1.5 Altruistic donation of non-regenerative
		organs by incompetent minors		75
		3.4.4.2 Summary		76
3.4.5		Clause 7.4		76
		3.4.5.1 HLA tissue typing for the benefit of a parent		76
		3.4.5.1.1	Clinical considerations	77
		3.4.5.1.2	Ethical considerations	78
		3.4.5.1.3	Summary	79
3.4.6		Clause 7.6		79
3.5	Additional justifications for restraint?			80
	3.5.1 Positive (moral) duty on parents			80
	3.5.2 Non-medical selection and the slippery slope			81
	3.5.3 Saviour foetuses			82
3.6	Other jurisdictions			83
	3.6.1 Norway			83
	3.6.2 Netherlands			84
	3.6.3 Denmark			84
	3.6.4 Sweden			84
	3.6.5 Victoria, Australia			85
	3.6.6 United Kingdom			85
	3.6.7 European Society for Human Reproduction and
	Embryology (ESHRE)			85
	3.6.8 Summary			85

Preimplantation genetic diagnosis (PGD) constitutes one of the most significant medical innovations of the last two decades in the area of assisted reproductive technology. The information derived from the genetic analysis of cells aspirated from an embryo created by in vitro fertilisation (IVF) may be used for diverse purposes, all of which may influence the decision as to which embryos should be implanted, and which discarded. With the introduction of the Human Assisted Reproductive Technology (HART) Act 2004, the performance of PGD is now subject to legislative and regulatory restraint. The purpose of this report is to consider extensions to the current scope of permissible PGD in New Zealand, and to determine the effect of the HART Act 2004 provisions on decision-making in this area.

PGD was first performed to determine the sex of embryos at risk of inheriting an X-linked condition. As the technology has become more sophisticated, it has become possible to determine the precise location of many genetic mutations and to develop genetic tests capable of diagnosing the presence of such mutations. At its simplest, PGD provides an opportunity for parents and clinicians to avoid the birth of a child who may be seriously impaired as a result of a familial single gene or familial chromosomal disorder. This category of PGD has been declared an ‘established procedure’ under the HART Act 2004 and may be carried out as a routine clinical procedure.1 PGD may also be used to screen embryos for numerical chromosomal abnormalities in the case of women who are of advanced reproductive age or who have had recurrent implantation failures or miscarriages. This category of PGD, which has also been declared to be an established procedure, permits the negative selection of embryos with chromosomal abnormalities which may threaten successful implantation and gestation. This type of PGD, commonly referred to as aneuploidy screening, constitutes the greatest demand for PGD and has largely escaped controversy.2 Prospective parents undergoing aneuploidy screening are simply trying to achieve a successful pregnancy and birth, rather than selecting against, or in favour of, a particular trait.

Beyond PGD simpliciter, PGD may be utilised for a multiplicity of purposes. For example, it may be performed to determine whether an embryo possesses the same tissue type as an existing sibling in need of a stem cell transplant. This latter application of PGD has stimulated vigorous international debate, particularly where the prospective embryos are not at risk of inheriting a genetic disorder. Testing for disorders which confer susceptibility, rather than a certainty, of developing a genetically-based condition is another example of an extended application of PGD. It too has engendered significant discussion because an individual may never develop the particular disorder or, even if they do, may live many years before the disorder becomes apparent. PGD can also reveal not only whether an embryo has a particular

genetic mutation which will manifest in disease, but also whether the embryo is a healthy carrier of the mutation. Healthy carriers of a familial mutation do not, with some exceptions, have any physical manifestation of the disorder, but may transmit the genetic disorder to the next generation. Hence, selection against healthy carrier embryos is controversial because it eliminates healthy embryos rather than embryos which would result in an affected child.

The advent of preimplantation genetic haplotyping (PGH) signals a further scientific advance in the area of preimplantation genetic testing. The procedure is reportedly more accurate than PGD. Significantly, PGH does not require that the precise details of a genetic mutation are known in advance. All that is required is knowledge of the region on a particular chromosome associated with a specific genetic mutation which results in a genetic disorder. With the introduction of PGH the number of single gene disorders that may be detected at the preimplantation stage has multiplied. In some instances, it is possible to distinguish embryos which are healthy carriers of a defective gene where it was previously not possible. In the case of a disorder such as Duchenne muscular dystrophy, an X-linked recessive disorder, PGD currently requires selection against all male embryos. With PGH, it is possible to determine which of the male embryos are affected and which are not. This in turn increases the number of embryos suitable for transfer and the success rate of a PGH cycle.3 PGH can also distinguish which female embryos are healthy carrier embryos of the mutation and which are healthy non-carriers.4 In the future whole genome screening, which could provide a complete genetic profile with the use of microarray technology, may be possible if current technical problems can be overcome.5 Progress in this area will provide significantly more scope for choosing embryos based on genetic characteristics.

The provision of PGD in New Zealand is still in its infancy, the first cycle only being performed towards the end of 2005.6 The HART Act 2004, the Human Assisted Reproductive Technology (HART) Order 2005 and the Guidelines on Preimplantation Genetic Diagnosis (2005) have established the lawful parameters of this relatively new medical technology.An in-depth analysis of these regulatory initiatives was undertaken in a prior report.7 The current regulatory framework is, in some respects, conservative in comparison to some other common law jurisdictions.8 The only applications of PGD permitted in New Zealand are strictly therapeutic, as understood in the narrow sense of the term, and they may only be undertaken to prevent the transmission of serious genetic disorders. The regulatory regime reflects an approach that permits PGD in the least controversial circumstances when it is generally perceived to be a medical imperative. However the current regulatory framework for PGD is not static. Regulatory mechanisms exist which enable the statutory Advisory Committee on Assisted Reproductive Technology (ACART) to restrict, or extend, the boundaries of PGD in New Zealand.

In view of developments in science and in other jurisdictions, it is likely that there will be a demand to extend the current ambit of the regulatory framework. Extending, or refusing to extend the current parameters for PGD will require a clear articulation of how the principles declared in the HART Act 2004 which govern decision-making in this area are to be applied.9

This report examines the conducting of PGD in areas which would broaden the existing regulatory scheme. In the following section an analysis of the HART Act 2004, and in particular the purposes and principles of the Act, will be undertaken to provide a foundation for the substantive examination of expansions to PGD in the following sections. The expansions discussed in sections 3 and 4 involve human leukocyte antigen (HLA) tissue typing and negative selection of healthy carrier embryos, respectively. In a field of rapid scientific progress, the last section in this report provides an update regarding the most recent development in the field of PGD: preimplantation genetic haplotyping (PGH).

It has been observed that the extent to which the use of genetic technology is determined by Parliament reflects the underlying public health and social policy agenda of a particular government.10 The introduction of the HART Act 2004 has signalled that human assisted reproduction is no longer an area of medicine regulated simply by professional self-regulation and the applicable general medical law; instead, it is now subject to a specific legislative scheme.

This report will argue that, with the establishment of the HART Act 2004, the New Zealand Government has established a mid-ground philosophy which on the one hand eschews radical reproductive liberty but on the other seeks to secure the benefits of assisted reproductive technology for ‘individuals and for society in general’ within a protective framework. Arguably, Parliament has opted for a flexible regime which may keep pace with progress and which requires dialogue with the public, whilst prohibiting what are deemed to be ‘unacceptable’ procedures or research. However, it is argued in this report that the objectives and purposes of the Act still support a presumption of reproductive liberty as the starting point when determining the appropriate parameters of assisted reproductive procedures such as PGD.

A brief outline of the current regulatory framework will be provided. However, the focus of this section is an analysis of the relevant purposes, principles and corresponding duties contained in the HART Act 2004, before the report moves on to consider expansions to the current regulatory framework for PGD in sections 3 and 4.

The HART Act 2004 establishes certain prohibitions such as the ban on reproductive cloning and germline genetic modification. In all other respects, the role of determining and advising what restrictions should be imposed on the use of reproductive genetic technology, in particular PGD, has been delegated to the statutory advisory body created under the Act, ACART.

The Act creates three categories of assisted reproductive procedures. The first encompasses procedures which are statutorily prohibited, such as PGD for social sex selection.11 The second category comprises procedures which are regulated and require the approval of the Ethics Committee on Assisted Reproductive Technology (ECART) in accordance with guidelines formulated by ACART before they may be performed.12 The third category constitutes activities which have been declared by Order in Council to be established procedures.13 Established procedures are routine clinical procedures that may be carried out without external scrutiny.

The Act provides no express guidance in relation to PGD with one exception. The conducting of PGD to diagnose and select on the grounds of sex in the absence of an X-linked condition is prohibited.14 This is a clear indication from Parliament that PGD should not extend to the selection of nondisease-related traits.

HLA tissue typing is currently a regulated procedure under the Act and applications may only be approved by ECART in accordance with the Guidelines on Preimplantation Genetic Diagnosis.15 HLA tissue typing to enable the selection of an embryo which has a compatible tissue type with an existing sick sibling in need of a stem cell transplant is permitted on a case-by-case basis according to specified criteria. However performing tissue typing is prohibited unless the embryos are at risk of inheriting a genetic disorder for which there is a test available.

PGD for familial single gene disorders, familial sex-linked disorders and familial chromosomal and non-familial chromosomal disorders in restricted circumstances are currently established procedures under the provisions of the HART Order 2005.16 Selection against healthy carrier embryos was not considered in the public consultation on PGD prior to the drafting of the PGD Guidelines, and is not expressly referred to in the HART Order 2005.17 Consequently it is unclear whether selection against healthy carrier embryos is permitted as a routine procedure under the Order.

It has been argued elsewhere that performing PGD for late-onset susceptibility disorders is permitted under the current established procedures category, although this does not appear to have been intentional on the part of the policy-makers.18 Whilst the merits of permitting PGD for susceptibility disorders has not been debated in New Zealand, the wording of the established procedures order appears

to be sufficiently broad to encompass PGD for lower-penetrance disorders as an established procedure.

As already indicated, this analysis is concerned with extensions to the regulatory framework in the areas of HLA tissue typing and selection against unaffected carrier embryos. However, a substantive analysis of these issues cannot be undertaken without first addressing the implications of the HART Act 2004. Consequently, the report now examines the objectives and purposes of the Act, and the duties imposed by the principles declared in the Act.

Section 3 of the HART Act 2004 articulates six distinct purposes. Additionally, a set of principles is provided which must guide persons exercising powers or performing functions under the Act if relevant to the particular power or function being exercised. Taken together, these objectives and principles do not overtly reveal an underlying principle or approach which is to be applied to human assisted reproductive technology. To distil an overriding principle necessitates careful dissection of the relevant purposes and principles of the Act.

Section 5(1) of the Interpretation Act 1999 states that ‘the meaning of an enactment must be ascertained from its text and in the light of its purpose’. The objectives of the HART Act 2004 may be condensed down to four main themes.19 The first is to secure the benefits of assisted reproductive technology and research within a framework which protects and promotes the ‘health, safety, dignity and rights of all individuals’, particularly those of women and children, in the use of such technologies (s 3(a)).20 The second is to prohibit‘unacceptable’ assisted reproductive procedures and research including certain commercial transactions relating to human reproduction such as the sale of human embryos or gametes (ss 3(b) and 3(c)). The third is to establish a flexible regulatory framework which delegates policy-making and regulatory authority to the two statutory bodies, ACART and ECART (ss 3(d), 3(e), 32, and 35). The fourth objective is to establish an information-keeping regime to ensure that people born from donated embryos or cells can find out about their genetic origins (s 3(f)). It is the first objective with which this analysis is concerned.

As already observed, the New Zealand Parliament has conferred on ACART the authority to determine and provide advice as to what constitutes permissible assisted reproductive procedures in New Zealand. When regulating contentious issues it is helpful, and often necessary, to adopt an overarching principle or set of principles that informs and supports the conclusions reached. Section 4 of the HART Act 2004 provides seven principles which must guide all persons (which implicitly includes ACART and ECART) who are exercising relevant powers or performing relevant

functions under the Act. (Emphasis added.) The principles relevant to this discussion are as follows:

The principles apply to the full range of human assisted reproductive procedures and human reproductive research. The legislation encompasses activities such as human embryonic research, human cloning, the supply of embryos and gametes, and other related activities, so the principles are necessarily generic. Whilst these principles are intended to provide guidance for policy-makers, their generic nature means that their application to a particular issue may support a variety of outcomes. When considering the legitimacy of the current regulatory restraints on PGD, and extensions to the framework, an in-depth analysis of the first purpose and the principles contained in the Act is necessary.

The first purpose of the Act refers to securing the benefits of assisted reproduction for individuals and for society in general by taking appropriate measures to protect and promote the health, safety, dignity and rights of all individuals. The full text of section 3(a) provides:

(a) to secure the benefits of assisted reproductive procedures, established procedures, and human reproductive research for individuals and for society in general by taking appropriate measures for the protection and promotion of the health, safety, dignity, and rights

of all individuals, but particularly those of women and children, in the use of these procedures and research.

Whilst the concept of health and safety are self-explanatory, the concepts of ‘dignity’ and ‘rights’ beg closer analysis. Both of these are explored in greater detail before attention is turned to the principles provided in the Act.

The promotion and protection of human dignity is a stalwart principle in international instruments as a criterion for guiding policy-making in the area of human rights as well as that of controversial scientific advances.21 This trend to incorporate the principle of human dignity into legislative instruments is evident in the HART Act 2004; but it is not defined, nor is it clear how it is to be applied.

The traditional human rights informed view of human dignity ascribes to the inherent worth of an individual, recognising a right to individual autonomy and the right to self-determination.22 Whilst autonomy is taken by many to be a core component of the concept of dignity, a broader concept of human dignity has been articulated by Justice Iacobucci of the Supreme Court of Canada:

Human dignity means that an individual or group feels self-respect and self-worth. It is concerned with physical and psychological integrity and empowerment.23

The problem with the concept of human dignity is the inherent difficulty in determining what it is and how respect for human dignity is best achieved. Human dignity is an amorphous concept, which changes according to the diverse perspectives held by various groups in society.24 It is difficult to attribute a precise meaning to the concept even in the particular context of the HART Act 2004. Dignity may be invoked to justify alternative sides of the same argument. For example, some would argue that to select an embryo on the basis of defined genetic characteristics is an inappropriate instrumentalisation and an affront to the prospective child’s dignity. Others may counter that to arbitrarily restrict parents from making decisions which they perceive would enhance the quality of life of their child and family is an affront to their personal dignity and autonomy.

It has been claimed that, in the light of new genetic technologies, human dignity is increasingly used ‘as a form of general condemnation and as blanket justification for regulatory restraint’.25 The use of human dignity as a criterion for policy-making has been described by at least one commentator as a ‘useless concept’26 and its relevance in bioethical discourse has been questioned.27 It has been argued that often

the use of human dignity seems to amount to little more than an articulation of a general social unease with a given technology.28

Whilst human dignity may support the right of an individual to make autonomous choices, dignity may also be used as a means of restraint. In this latter context, the use of dignity as a criterion is ‘meant to reflect a broad social or moral position that a particular type of activity is contrary to public morality or the collective good’.29 The result is that an undefined notion of human dignity may determine whether a particular scientific activity is acceptable depending on whether it offends human dignity, rather than on the basis of tangible harms that may result from it.30 It is generally conceded that although the concept of human dignity is of great importance, it is not helpful as a sole guiding principle when determining the appropriate scope of reprogenetic technology. As one commentator observed:

... it is something of a loose cannon, open to abuse and misinterpretation; it can oversimplify complex questions; and it can encourage a paternalism that is incompatible with the spirit of self-determination that informs the mainstream of human rights thinking.31

Although the concept of respect for human dignity has been described as ‘comprehensively vague’,32 most consider that it has a place in discussions involving new genetic technologies.33 It has been observed that the idea of human dignity may be of greatest assistance when it is used as a vehicle for exploring differing philosophical approaches in a pluralistic society.34 Such an approach considers the different values held and deemed important by different individuals or groups, and essentially involves having respect for others. It is argued here that, when considering the performance of assisted reproductive procedures under the HART Act 2004, competing claims based on dignity must be fully articulated and weighed against the relevant interests at stake or by reference to an overriding principle.

As already indicated, the first purpose declared in the HART Act 2004 is to secure the benefits of assisted reproductive technology for individuals and society by taking measures to protect and promote the ‘rights of all individuals’ in the use of assisted reproduction. The Act does not elaborate on the nature of applicable rights. Arguably a highly relevant right in this context is the claimed right to reproductive liberty.

However, it is not sufficient to simply assert that reproductive liberty is preserved under the Act without an analysis of the basis of the right and whether it is applicable to assisted reproduction.

One of the political characteristics of a liberal democracy is the philosophy that citizens should be free to conduct their lives without interference by the State unless such interference is necessary to avoid harm to others.35 This principle effectively means that individuals ‘should be free to make their own choices in the light of their own values whether or not these are acceptable to the majority’, unless there is an adequate justification for the State to intervene.36

The liberal democratic presumption encompasses two central elements, autonomy and liberty. Respect for autonomy is premised on the idea that an individual’s best interests are generally best served by allowing a person to make autonomous decisions; and individuals are assumed to be able to judge, better than anyone else, what constitutes their own interests.37 Autonomy requires not only ‘independence from controlling influences’, but also the ‘capacity for intentional action’.38

It stands to reason that when an individual’s liberty is curbed, so too is that person’s autonomy and, potentially, the capacity to further their relevant interests.39 This is generally perceived to constitute a ‘harm’, and is the basis for the harm principle articulated by the American philosopher Joel Feinberg. The harm principle provides that

state interference with a citizen’s behaviour tends to be morally justified when it is reasonably necessary ... to prevent harm or the unreasonable risk of harm to parties other than the person interfered with.40

Given the liberal presumption, it has been argued that the burden of justifying restrictions on liberty is placed on ‘those who would deny liberty, not on those who would exercise it’.41 The concept of reproductive liberty is subsumed within the liberal democratic presumption.

The basis of reproductive liberty, which had its genesis in the reproductive rights movement of the twentieth century, is the right claimed by women to control their reproductive capacities and to make reproductive choices.42 The right to reproductive liberty was asserted as the moral justification for permitting access to lawful termination of pregnancy in the abortion debates of the mid 1900s. The right to reproductive liberty was established as a legal right with the acknowledgment by the legislature of a woman’s right to a lawful abortion.43 In the context of abortion, reproductive liberty in a liberal, rights-based society has been acknowledged as a basic freedom.44

Reproductive liberty is a facet of both the liberal democratic presumption and liberty in general. The overlap between reproductive liberty, human dignity and democracy is illustrated in the following words of Dworkin:

The right of procreative autonomy has an important place ... in Western political culture ... The most important feature of that culture is a belief in individual human dignity: that people have the moral right – and the moral responsibility

– to confront the most fundamental questions about the meaning and value of their own lives for themselves, answering to their own consciences and convictions

... The principle of procreative autonomy, in a broad sense, is embedded in any genuinely democratic culture.45

Although the principle of reproductive liberty has been established in the context of abortion and the right to choose, closer analysis is required to determine whether it is automatically applicable to assisted reproductive technology. Reproductive liberty is generally accepted as a negative right against interference by the state or others with regard to reproductive decisions. In the modern context, reproductive liberty has been used as a moral argument in favour of permitting the use of reprogenetic technologies to assist parents to have ‘healthy, biologically related offspring’.46 It is argued that the right in a liberal democratic society to reproductive liberty is applicable to the performance of assisted reproductive procedures such as PGD, and is implicitly adopted in the purpose declared in section 3(a) of the Act. Before addressing this latter issue, the nature of the right to reproductive liberty established in relation to abortion is first considered.

Although reproductive liberty has been recognised as an important freedom, which provides a strong argument in favour of a woman’s right to choose whether or not to continue a pregnancy, it is not absolute. In the context of abortion, it is relatively common to hear a person refer to ‘abortion on demand’. Yet this is based on a widely held misapprehension. In New Zealand, abortion is lawful up until the twentieth week of pregnancy, but only where continuing the pregnancy would pose a serious risk to the life, or to the physical or mental health, of the woman, or where there is a substantial risk of serious handicap in the child.47 The law reflects a view that the further developed a foetus has become, the more protection it is owed. Late abortions carried out in the second trimester for perceived trivial grounds have attracted scrutiny both internationally and domestically.48

Clearly there is evidence of a widely held view that the more advanced a pregnancy is, the more compelling a reason must be to justify termination.49 Although the intrinsic value of reproductive liberty has been a powerful argument in favour of permitting abortion, it is a concept which is limited by the dictates of what is perceived to be broadly acceptable by society and the law.

It is plausible to argue that the principle of choice and reproductive liberty provides a strong moral basis for claims in relation to the desire to conceive a child, just as it deserves respect in relation to the desire not to have a child.50 However, it must be acknowledged that, although it may exist, a right is not necessarily unqualified. The Report of the United Kingdom’s House of Commons Science and Technology Committee endorsed the view that achieving a pregnancy with the assistance of reproductive technology is an exercise of reproductive freedom.51 However, the Committee also agreed with the view that reproductive freedom was not absolute.52 Reproductive freedom does not necessarily confer positive rights of access to assisted reproductive procedures. But it does mean that‘the principles of choice and autonomy are principles or values that, among others, must be seriously considered’.53 John Robertson has cogently argued that:

... recognizing procreative liberty as a moral or legal right or important freedom does not mean that it is absolute, but rather that there is a strong presumption in its favor, with the burden on opponents to show that there is a good case for limiting it. Many critics, however, assume that claims of procreative liberty are claims of an inalienable or absolute right.54 But a right can be inalienable – not transferable to others – without being absolute. And no serious proponents of procreative liberty argue that it is absolute and can never be limited. Rather, the debate is (or should be) about whether particular exercises or classes of exercise of the right pose risks of such harm to others that they might justly be limited.55

The approach adopted in this analysis is that the moral arguments which support reproductive liberty are as valid in respect of conceiving a child using assisted reproductive technology as they are in respect of supporting a woman’s right to choose to terminate an unwanted pregnancy. However, the concept of reproductive liberty does not confer unfettered choice. Rather, it signals the importance of the interests at hand. A presumption of reproductive liberty is arguably consistent with the objectives provided in the HART Act 2004. These expressly focus on protecting and promoting the interests of the individuals involved, particularly women and the putative children. The question is, to what extent should reproductive liberty be restrained and why? By virtue of the harm principle, legitimate restrictions on PGD require not only that a risk of harm must be demonstrated, but that it is of ‘sufficient magnitude to justify the harm caused to those whose liberty interest is curtailed’.56

Other rights which may be relevant to section 3(a) of the HART Act 2004 include disability rights. Some disability rights proponents have voiced concern that PGD devalues people with disabilities. The New Zealand Bill of Rights Act (NZBORA) 1990 provides that everyone has the right to freedom from discrimination on the

grounds of discrimination in the Human Rights Act 1993, which include the right not to be discriminated against on the grounds of disability.57 The NZBORA 1990 applies to every person or body in the performance of any public function, power or duty conferred or imposed on that body by or pursuant to law.58 Consequently, the right to freedom from discrimination is an established legal right and persons exercising powers under the HART Act 2004 are subject to the provisions of the NZBORA 1990.

Although there are several strands to the concerns held by a subsection of disability rights advocates in regard to PGD and prenatal testing, the relevant concern for this section of the Act relates to discrimination.59 It is frequently observed that a ‘major problem with having a disability is not the disability per se, but the discrimination the disabled face for themselves and their families’.60 It follows that disability that results principally from impairment should be distinguished from disability that results from ‘a socially inadequate or discriminatory response to impairment’.61 Consequently, the experience of disability extends beyond physical limitations to the way that society responds to the needs of people with particular disabilities.

This is highly relevant. It has been said that the ‘choices’ provided by new genetic technologies may be illusory, given that

society does not truly accept children with disabilities or provide assistance for their nurturance. Thus, a woman may see no realistic alternative to diagnosing and aborting a fetus likely to be affected, 62

or, by analogy, engaging in PGD. In this context, it is important to consider that choices may be made on grounds that ‘reflect a particularly inflexible social structure rather than the particular severity of a medical condition’.63 There is also a resistance to PGD by those who perceive that permitting embryo diagnosis devalues and expresses discriminatory attitudes towards those already born with impairments.64 Yet the fact remains that not all the difficulties associated with disability are socially constructed; and parents may legitimately seek to avoid having their children experience significant functional limitations. Nor is it incompatible to wish on the one hand to avoid transmitting a genetic mutation, but on the other to support attempts to minimise discrimination towards the disabled and to support policies which assist the disabled to achieve their potential.65 As one commentator has noted:

for parents to wish to avoid the harms of impairment that are accentuated by lack of social support is not necessarily to collude in discriminatory practices, where society cannot be expected absolutely, rather than reasonably, to provide social support, given the diverse and conflicting interests that it is required to accommodate.66

The current policy in New Zealand permits prospective parents to undertake PGD if they are at risk of transmitting a serious genetic disorder. That decision is in keeping with the grounds for lawful abortion on the grounds of foetal abnormality. What is apparent is that there should not be an assumption on the part of providers or counsellors that parents must act to avoid disability, or make certain choices. Rather, families should be supported in decision-making with non-directive counselling and sufficient understanding of the relevant disorder.

Under section 4 of the HART Act 2004 all persons exercising powers or performing functions pursuant to the Act must be guided by the principles declared in the Act. The first of these seven principles provides that the health and well-being of children born as a result of an assisted reproductive procedure or an established procedure should be an important consideration in all decisions about that procedure.

Clinicians, as well as policy-makers, have a specific responsibility concerning the interests of the future child. The primary aim of assisted reproductive technology, including PGD, is the achievement of a healthy live birth, yet the relative importance of the interests of the prospective child is not clearly established. The wording of the health and well-being principle in the Act deliberately eschews the usual paramount importance attributed to a child’s welfare in family law.67 Although the HART Bill (as amended by Supplementary Order Paper, No. 80, 2003) initially required that the health and well-being of children born as a result of assisted reproduction should be ‘paramount’ in all decisions about procedures, this provision was altered by the Health Select Committee during the legislative process.

The paramount welfare principle was rejected because it would narrowly circumscribe the performance of any procedure which may pose a physical or psychological risk to the prospective child. It could even be interpreted as implying that ‘one should not knowingly and intentionally bring a child into the world in less than ideal circumstances’.68 Because assisted reproductive technology necessarily entails greater risks than those associated with natural conception,69 the paramount provision could prevent the approval of assisted reproductive procedures because of those heightened risks.70 Similarly, it has been observed that, if the paramount welfare principle were consistently applied to all instances of reproduction, it would ‘exclude the overwhelming majority of the population from procreation’.71

The polar opposite of the maximum risk principle is the minimum risk principle. The application of this principle would preclude the performance of an assisted reproductive procedure only when there is a serious risk that the life of the prospective child would be so miserable that it would not be a life worth living. Such a standard

would mean that the range of permissible procedures would be extremely broad regardless of risk. It attributes enormous importance to reproductive autonomy and parental autonomy.

The welfare principle declared in the HART Act 2004 suggests that Parliament intends an intermediate position between these two extremes: it does not ascribe paramountcy to the future child’s welfare, but still requires that the future child’s health and well-being should be an important consideration. This avoids outcomes that would be counter-intuitive to many, such as preventing procedures from being undertaken on the basis of a risk so small as to be negligible on the one hand, or permitting procedures to be performed impervious to the risks posed to the future child on the other.

Significantly, ‘health and well-being’ would appear to encompass not only physical well-being, but also the social, emotional, psychological and cognitive aspects of a child’s welfare. This potentially provides greater scope for expanding the ambit of PGD, by permitting a range of factors to be considered – not just physical considerations. What constitutes sufficient health and well-being is an open question. It may simply constitute ‘the abilities that are required for an individual to enjoy a normal range of opportunity in society’,72 as opposed to a life that is ‘significantly deficient in one or more major respects that generally make human lives valuable and worth living’.73

The second principle of the HART Act 2004 provides that ‘the human health, safety, and dignity of present and future generations should be preserved and promoted’.74 (Emphasis added.) It appears expressly to incorporate the principle of intergenerational justice into the principles of the HART Act 2004.

The application of the principle of intergenerational justice to reproductive decision- making has emerged over the last decade and a half. Adherence to this principle requires a consideration of the interests of future generations when making current decisions75 and is, essentially, the duty to prevent intergenerational harm.76

The principle of intergenerational justice is open to wide interpretation. If given a radical interpretation, this requirement may be interpreted as precluding persons from knowingly passing on deleterious genes to their offspring and could justify the prevention, either by legal means or by overt pressure on prospective parents, of the births of children with severe genetic disease. Applying this interpretation, failure to avoid an affected pregnancy by undertaking PGD, or knowingly carrying an affected pregnancy, may contravene the concept of intergenerational justice. Such an outcome was foreseen by the commentator who made the following statement:

the completion of the human genome project will provide a basis for acting on a moral obligation for future generations, a claim that has appeared weak in the past. A generation with such knowledge who neglected to use it to minimize the risks in reproduction could hardly be said to respect the requirements of intergenerational justice.77

Applying the concept of intergenerational justice in this way is to assert that parents who have a disabled child are harming not only that child, but also the community and potentially successive generations. It has been argued that the advances in reproductive genetics

both reflect and reinforce the negative attitudes of our society towards those with disabilities. Indeed, medical genetics may add a new dimension if genetic disorder came to be seen as a matter of choice rather than of fate.78

Such a position would represent the imposition of a coercive eugenic philosophy under the Act. Government imposed eugenics, a practice perceived as being both abhorrent and a breach of civil liberties, is arguably inconsistent with the intention of the Act which preserves individual rights. The purpose of the Act, which is to secure the benefits of assisted reproductive technology for individuals and society by providing for the protection and promotion of the health, safety, dignity and rights of all individuals, particularly women and children, in the use of these procedures, does not support such an extreme interpretation of this provision. It is clear from this purpose and the principles of the Act that the legislation is most concerned with protecting the interests and rights of those directly involved in assisted reproduction, that is the future child and the prospective parents, rather than imposing a genetic blueprint for society.79 Consequently, a less extreme application of the concept of intergenerational justice would ascribe more emphasis on individual rights and is more sympathetic to the overall philosophy of the HART Act 2004.

It is argued that section 4(b) acknowledges that assisted reproductive procedures can have intergenerational effects, and requires that the health, safety and dignity of both current and future generations be deemed relevant in the exercise of a power or performance of a function under the Act. Whilst the current regulatory framework signals that the prevention of the birth of children suffering from serious disorders is an acceptable reproductive choice for some prospective parents, it is not a government-imposed public health requirement.

Although the concept of intergenerational justice may not be used as a basis for requiring parents to make certain choices, it may and has been used to justify permitting certain choices, such as sex selection.80 Although sex selection is prohibited under the Act, an argument in favour of sex selection on the grounds of intergenerational justice has been made.

This claim is predicated on the grounds that if it is accepted that one of the goals of assisted reproductive technology is to improve the objective well-being in a future child (by avoiding the birth of a disabled child), then the prevention of physical illness should not be the sole goal in the use of assisted reproductive technology. Rather, it is also justifiable to use such procedures when a future child could suffer poor levels of objective well-being not only as a result of medical factors, but also as a result of cognitive, emotional and social factors. This could occur when a child is exposed to harm ‘created because of the gender hostility of a specific social environment’.81 If the objective well-being of children and parents is reduced, the existing and new children will be objectively harmed. This will apply to their children, and thus to a diminution of the objective well-being of future generations. In this way, the concept of intergenerational justice in section 4(b) of the Act may be used to justify an expansion of the range of reproductive choices, when they are construed as enhancing or protecting the well-being of future children.82

The third principle of the HART Act 2004 provides that ‘while all persons are affected by assisted reproductive procedures and established procedures, women, more than men, are directly and significantly affected by their application, and the health and well-being of women must be protected in the use of these procedures’.

This provision was drawn from one of the core principles provided by the Canadian Assisted Human Reproduction Act 2004.83 However, in contrast to the HART Act 2004, the Canadian legislation expressly prioritises the interests of the child to be born by providing that ‘the health and well-being of children born through the application of assisted human reproductive technologies must be given priority in all decisions respecting their use’.84

Arguably, section 4(c) of the HART Act 2004 does not seek to prioritise the interests of the women involved. It merely seeks to signal the fact that women, regardless of the circumstances which have required them to seek assisted reproduction, are necessarily required to undertake the greatest burden of assisted reproduction. Consequently their health and well-being must be safeguarded in the performance of assisted reproductive procedures.85 The justification for the principle in the Canadian framework was as follows:

Equality should be promoted among women and men; however, reproductive policy development should not proceed as though reproduction affects women and men in the same way. The physical and social burdens and risks of reproduction are borne primarily by women. These realities should be acknowledged and reflected in reproductive policy.86

Although it is unavoidable that women carry the greatest physical burden of IVF, in the context of PGD there may be additional considerations. PGD may be necessary because the man is a carrier of an autosomal dominant disorder. Because of this, he may feel significant guilt that his partner has to go through an invasive and difficult procedure. There is also mounting evidence that men’s reproductive health needs are insufficiently provided for in health policies in general.87 Whilst section 4(c) expressly provides that the health and well-being of women must be protected, it should not be seen to diminish the effects that assisted reproduction may have on men.

It is argued that these principles flag the competing interests which must be taken into account under the Act, but do not elevate the interests of one party.

Additional principles in the Act include the principle that no procedure should be performed unless an individual has provided informed consent.88 This principle merely restates the general law with regard to medical treatment and, at first glance, appears unremarkable. However, in the context of assisted reproduction, decision- making involving in vitro embryos is seldom a solitary endeavour.

It is an open question whether PGD, for example, requires the consent of only one or both prospective parents, or whether implantation of an embryo may occur if the prospective father withdraws consent. Although these issues beg further analysis, they are beyond the scope of this report, which focuses on PGD in conjunction with HLA tissue typing, and negative selection of carrier embryos.

The Act also provides a principle regarding donor offspring. However this principle is not relevant in the context of the current discussion. A further principle requires that the ‘needs, values, and beliefs of Mäori should be considered and treated with respect’. A comprehensive analysis of PGD from a Mäori perspective was undertaken in a prior report, and so will not be repeated here.89 Another relevant principle for this discussion is the final principle provided in the Act. It requires that the different perspectives in society are considered and treated with respect.

Section 4(g) of the Act declares the principle that ‘the different ethical, spiritual, and cultural perspectives in society should be considered and treated with respect’. This last principle is significant as it derogates from what has, for the most part, dealt with the interests of those directly involved in assisted reproduction, and moves to collective interests in society.

The principle contained in section 4(g) acknowledges the extreme diversity of opinion which exists in relation to assisted reproduction. Whilst differing perspectives may not be reconcilable, the Act requires the exploration of these perspectives

in a conscientious and meaningful way. However, in no way does it diminish the underlying purpose of the Act, which is to secure the benefits of advances in assisted reproduction within a protective framework.

Several perspectives are relevant when considering PGD and expansions to the regulatory framework. These include the differing perspectives on the moral status of the embryo. As this issue was canvassed in detail in a prior report, it will not be analysed further here.90 Another perspective equates the use of new reprogenetic technologies with the conducting of eugenics. It is alleged that the avoidance of genetic disorders through the use of reprogenetic technology may have a negative impact on society. These perspectives have been central in debates regarding the introduction of PGD simpliciter, and are relevant when contemplating expansions beyond.

When PGD was first introduced it was accompanied by an outpouring of eugenic concerns. This was, in part, a reaction rooted in the legacy left by the systematic government-imposed discrimination towards individuals on the basis of genetic characteristics in the late nineteenth and early twentieth centuries. The eugenics movement subscribed to the idea that certain characteristics such as intelligence were hereditary. Consequently, those considered to have suitably good heritable characteristics were encouraged to have more children, and others were discouraged or actively prevented from parenting.91

New Zealand was not immune to eugenic influences when the Mental Defectives Amendment Bill was introduced into Parliament in 1928.92 The Bill contained provisions which, if enacted, would have permitted the compulsory sterilisation of people judged to be mentally defective. It also restricted the right of persons deemed mentally defective to marry. These provisions were met with vehement parliamentary opposition. Although the Bill was eventually passed, these clauses were not included.93 It has been claimed that ‘New Zealand was alone in the economically developing world in rejecting a formal proposition for the sterilization if not castration of people designated socially as “unfit”’.94

Some commentators have argued that as a result of ‘social pressures and eugenic attitudes held by clinical geneticists in most countries, it [PGD] results in eugenic outcomes even though no state coercion is involved’.95 Because PGD concerns embryos rather than established pregnancies, it is distinguishable from prenatal testing in ‘ethical, legal, social and psychological terms’.96 Consequently, the scope for selection is arguably greater as is the possibility of coercion and reduced choice.97

Other commentators have cautioned that we should take care not to misuse eugenic events, such as the Nazi experience, which may in fact have very little to do with

an individual’s or couple’s decision not to have a child with a severe disease.98 The World Health Organisation (WHO) has provided the following definition of eugenics:

A coercive policy intended to further a reproductive goal, against the rights, freedoms, and choices of the individual ... Cultures or medical settings may be implicitly coercive and are aware of the need for vigilance against tacit coercion, but considered such problems as part of the general social context rather than as eugenic programs.

Under the above definition, knowledge-based, goal-oriented individual or family choices to have a healthy baby do not constitute eugenics. Such choices are unlikely to affect the gene pool or to reduce the numbers of persons with disabilities. Most disabilities are not the results of chromosomal or single-gene disorders, and most babies born with a genetic disorder are born to families with no known risk for having a child with that condition.

Eugenics is directed against whole populations, whereas the work of today’s clinical geneticists is directed towards individuals and families. However, it is important to be aware that collective results of individual decisions could lead to social policies that discriminate against the minority who make different decisions and especially against persons with disabilities.99

Argumentsbasedoneugenicsignorethefactthat,forsomeparentsatriskoftransmitting what they consider are serious heritable diseases, PGD is a medical imperative and should be a matter of individual choice. PGD is not a State-imposed requirement. However, the provision of services and perceived coercion by professionals is very much a live issue. Eugenic concerns do not displace the presumption of reproductive liberty when considering expansions to PGD for disease-related genotypes. However, as is evident in the WHO report, eugenic concerns are relevant to the way in which PGD services are provided.

Crafting public policy on contentious issues, such as those raised by assisted reproductive technology and PGD where there is not only an absence of public consensus but also extremely polarised and strongly held views, requires more than an intuitive, personal response to complex issues. Mary Warnock’s characterisation of the difference between policy-making and intuitive private moral responses is compelling in this context:

The pub bore speaks intuitively ... Even if he has good reasons for his judgement that something is ‘disgusting’, he may not be able to articulate them ... His conclusion, that the thing is wrong, may be perfectly sound. But he makes the false assumption that his judgement should, or could, be instantly translated into a law which should govern everyone, and turn that which he is objecting to into a criminal offence. When people become legislators or politicians, they assume new responsibilities. They have specifically to exercise reason and caution in attempting to foresee the consequences for everyone, including minority groups, of the measures they are proposing ... Moreover, they owe a duty to be able to explain why they have come to the conclusion they have. They must be seen to have thought rationally; and in public circumstances this means that they be seen to have thought about the long-term consequences of what it is they propose. They must be seen to be steady and consistent in the stance they take, not only because they will probably advance their own careers if so perceived, but because steady and principled government is what is actually needed by society. So the overlap, or interplay, between the public and private comes at the place where principles are to be articulated, and the consequences for society as a whole openly taken into account.100

Clearly, the formulation of good social policy requires close examination of the issues involved, a rejection of rhetoric and dogma and a search for a shared value. Principles must be articulated and the consequences for society as a whole openly taken into account. This is what is required by the HART Act 2004.

Although the provision of PGD in New Zealand has become part of mainstream medicine, and may be carried out as an established procedure in some instances, it is still subject to regulatory restraint under the HART Act 2004. When considering the legitimacy of those restraints, and possible extensions to the framework, it is necessary to determine the effect of the objectives and principles contained in the Act.

The HART Act 2004 declares certain objectives and provides a list of principles which must guide both policy-makers and providers of fertility services. However, there is no clear articulation of the underlying principle or principles which should be applied in this context, nor of how the stated objectives and principles are to be balanced. With the introduction of the HART Act 2004, Parliament arguably has established a middle ground which on the one hand rejects radical reproductive liberty (which would render all reproductive decision-making a matter of personal conscience), but on the other hand seeks to secure the benefits of assisted reproduction within a protective framework.

Although the principle of reproductive liberty is not expressly stated or incorporated in the Act, the objectives and principles taken together do not preclude a presumption of reproductive liberty as a starting point. Rather, the first objective of the Act is to

protect and promote the health, safety, dignity and rights of all individuals, and of women and children in particular, in the use of assisted reproductive procedures. The purpose of the Act expressly refers to the promotion of the dignity and rights of individuals in the use of assisted reproductive technology, and clearly expresses a commitment to the preservation of individual rights. Reproductive liberty may be reconciled within the principles which expressly focus on the interests of the individuals involved, particularly women and the prospective children, and the perspectives of the community.

Reproductive liberty is an established principle in relation to natural conception. It is argued that it is equally applicable to assisted reproduction and is preserved by virtue of the first purpose declared in the Act. The moral arguments which support reproductive autonomy with regard to a woman’s right to abortion are equally valid with regard to the use of assisted reproductive technology to conceive a healthy, genetically related child. Reproductive autonomy is intimately associated with a woman’s right to make reproductive choices. In the context of PGD, decisions are generally those of the prospective parents, made on the basis of their combined genetic codes; it is seldom a solitary endeavour. In both contexts there are strong moral arguments in favour of respecting autonomy and values such as freedom of choice which underlie reproductive endeavours. Individual choices may not be universally endorsed, but this does not mean that certain activities should necessarily be prohibited. The principle of reproductive liberty does not confer a right to unfettered choice or access, but it signals the importance of the interests involved and the respect owed. The question is why and to what extent reproductive liberty should be limited.

It can be argued that when contemplating the current regulatory framework for PGD, and the expansion of the scope of permissible PGD, a presumption of reproductive liberty is the appropriate starting point. This position should then be scrutinised with reference to the principles set out in the Act.

Whilst it has been argued that human dignity is an elusive concept which has, in relation to scientific progress, been used to support various outcomes, dignity has traditionally been associated with an individual’s inherent right to autonomy and respect. The notions of human dignity and human rights are easily invoked to support various outcomes in relation to reprogenetic technology. Whilst they may be used as a justification for restraint, they may also be used in support of autonomous action. The reference to both ‘dignity’ and ‘rights’ in the Act supports the argument that the right to reproductive liberty, a freedom which is accepted as a fundamental human right to varying degrees in all liberal democracies, is not abrogated by the Act. However, claims based on dignity must be fully articulated and weighed against the relevant interests and principles at stake, including the right to reproductive liberty.

The principle regarding the welfare of the future child is notable in that it does not ascribe paramountcy to the health and well-being of a future child, a protection accorded a child in family law proceedings once born. Significantly, ‘health and well-being’ arguably encompasses not only physical well-being, but also the social, emotional, psychological and cognitive aspects of welfare. The well-being of a child is significantly affected by the family into which it is born. Consequently, the well-being of the family is integral to the well-being of the child. This may provide greater scope for expanding the ambit of PGD in certain circumstances.

The concept of intergenerational justice may support arguments for expanding the regulatory framework; indeed, a radical interpretation of the concept may require parents to use PGD and prenatal diagnosis where there is a known risk of harm to a future generation. However, this is inconsistent with the current public health and social policy agenda of New Zealand if it is accepted that the objective in the provision of reprogenetic technology is to enable access to treatment and to help at-risk people make fully informed, autonomous decisions. The principle of intergenerational justice should not be used to exert pressure on prospective parents to make certain choices as part of a public health or social policy agenda, as this is not consistent with the purposes of the Act.

The requirement that the health and well-being of women must be protected in the use of assisted reproductive technology acknowledges the central role played by women in assisted reproduction, but is arguably limited to the safe provision and use of assisted reproductive technology. Neither disability rights arguments nor eugenic concerns displace the presumption of reproductive liberty when considering expansions to PGD for disease-related genotypes. However these concerns are potently relevant to the way in which PGD services are provided. Whilst expanded reproductive choice in relation to heritable disease-related genotypes is to be welcomed, the obligation to engage in PGD, or to make certain choices, is another thing altogether.

The issue, for the purposes of this report, is whether the current limits on reproductive liberty in relation to HLA tissue typing and negative selection of carrier embryos may be justified, or whether the scope should be extended. The report is mindful that, on the basis of the harm principle, legitimate restrictions to PGD require not only that a reasonable risk of harm must be demonstrated, but also that it is of sufficient magnitude to justify curtailing the autonomy of those seeking PGD services.101

PGD in conjunction with human leukocyte antigen (HLA) tissue typing involves testing embryos to determine their compatibility as haematopoietic stem cell (HSC) donors for siblings suffering from life-threatening diseases. When a child is suffering from a congenital disease or neoplastic disorder which affects the formation of blood cells and/or the immune system, transplantation of HSCs such as those contained in umbilical cord blood or bone marrow is currently the best course of treatment for the affected child.102 HSC transplantation may also be indicated for a number of metabolic diseases such as adreno-leukodystrophy.103 When there is no HLA-identical donor available in the family, PGD can be used to select an embryo with the same HLA tissue type as the sick sibling.

The first applications of PGD in conjunction with HLA tissue typing in both the United States and the United Kingdom involved performing PGD to diagnose the presence of a deleterious genetic mutation (in the former case Fanconi anaemia and in the latter thalassaemia) in addition to carrying out HLA tissue typing on in vitro embryos. Performing PGD to create a child to save another has attracted considerable debate in itself as evidenced by the interest generated by these two cases. However, the distinction between performing preimplantation tissue typing as an adjunct to the diagnosis of a serious genetic condition and performing it solely to determine tissue compatibility with a seriously ill sibling has added another dimension to the controversy.

New Zealand has only recently begun to address these issues with the introduction of the Guidelines on Preimplantation Genetic Diagnosis in 2005.104 Although drafted by the ethical body which preceded the introduction of the HART Act 2004, the Guidelines now constitute ACART guidelines for the purposes of the Act.105

PGD in conjunction with HLA tissue typing is currently the only application of PGD that comes within the remit of ECART as a regulated activity. Pursuant to the Act, PGD with HLA tissue typing may only be performed with the prior written approval of ECART.106 Applications are assessed on a case-by-case basis. Ethical approval may only be given when the applicants meet the requirements prescribed in the Guidelines.107 Currently, the Guidelines restrict the performance of HLA tissue typing in conjunction with PGD to circumstances in which the live sibling is suffering from a familial single gene or sex-linked disorder, as well as providing significant other restraints. It is the substantive provisions of these Guidelines which are the focus of this section.

Before undertaking an analysis of the Guidelines, a brief background will be provided regarding the history of the donation of HSCs by a minor child to a sibling suffering from a severe, life-threatening disorder. General clinical considerations raised by embryonic HLA tissue typing and HSC transplantation will then be outlined. Following this, the provisions and implications of the current Guidelines will be examined. Because of the nature of the subject matter, this analysis necessarily requires a review of the legal position regarding the donation of tissue and organs by an incompetent minor to a sick sibling. The question addressed in this section is whether, given the presumption of reproductive liberty established in the previous section of this report, the restraints on HLA tissue typing provided in the Guidelines are justified. It will be argued that the Guidelines are ethically and legally problematic.

The complexity of the saviour sibling issue exists because of the breadth of interests implicated by the use of this new technology. These interests have been described by one commentator as including:

the rights of parents to be able to make reproductive decisions, the rights of the sick child to medical treatment and to hope, the rights of the donor child to be loved for themselves and to be free from exploitation, the ethics of tissue donations from incompetent individuals, the degree to which family autonomy will be upheld, and the rights of the broader community to have a say in the directions new science takes us.108

Sibling donation of HSCs is not a new medical technology. Nor is the intentional conception of HLA-matched sibling donors. Rather, it is the performance of these activities in the context of PGD that is new.

Prior to the advent of PGD, parents of children with severe, life-threatening diseases that could be cured by a HSC transplant attempted to conceive a healthy HLA- matched child naturally. The precursor to transplantation of HSCs from cord blood was transplantation of HSCs from bone marrow. The attempted conception of children to save siblings was practiced as early as 1987, and was achieved in some instances.109 The first successful allogeneic bone marrow transplant (i.e. bone marrow from another person) was carried out in 1968 when a five-month-old infant received HSCs from a sibling.110 When it became possible to diagnose Fanconi anaemia and HLA-type prenatally in the 1980s, it was reported that between 1985 and 1993 thirty- two pregnancies were conceived in the hopes of providing a donor child for a sibling with the disease.111 Some of these attempts failed whilst other couples were faced with aborting affected foetuses. In two cases healthy foetuses that were not HLA compatible with the sick sibling were terminated.

Allogeneic bone marrow transplantation is now an established therapy in the treatment of haematological malignancies, bone marrow failure syndromes, immunodeficiency states, and metabolic disorders.112 Because of the limitations associated with bone marrow transplantation, namely the lack of suitable donors, the risk of graft-versus- host disease and opportunistic infection, transplants using umbilical cord blood stem cells were first postulated as an alternative source of HSCs in the early 1980s.113

In 1988 the first successful umbilical cord blood transplant was undertaken for a child suffering from Fanconi anaemia.114 Twelve years later the first child conceived after successful PGD and HLA tissue typing was born in the United States. The parents wished to avoid the birth of a child affected by Fanconi anaemia, and to have a child who was a tissue match for their affected daughter. The six-year-old sibling underwent a successful cord blood transplant three weeks later.115 Since then the range of diseases and indications for which PGD for HLA matching could theoretically be used has grown considerably, as illustrated by the list provided at the end of this section. Although the conception of sibling donors has a long history, the use of PGD to diagnose tissue type is an innovation of the twentieth century and is strictly regulated in New Zealand. Before considering the nature of those restrictions, the following section provides a brief précis of the clinical context.

Any analysis of the Guidelines requires some appreciation of the clinical context. Whilst there are strong clinical reasons in favour of umbilical cord transplant from an HLA-matched sibling, other considerations must also be taken into account.

Transplantation of HSCs from umbilical cord blood is generally considered to be superior to bone marrow transplant, and transplantation of cord blood from an HLA-matched sibling even more so. The benefits of cord blood HSC transplantation (HSCT) include the diminished risk for the donor. The physical collection of stem cells from the umbilicus is a relatively safe and straightforward procedure, without the risks of general anaesthesia, bleeding or infection associated with bone marrow harvesting.

Most importantly, there is a lower incidence of acute and chronic graft-versus-host disease in the recipient in the case of sibling cord blood transplants compared with bone marrow transplants.116 Umbilical cord blood donors and recipients may not need to be HLA matched with the same rigour as for bone marrow transplants.117 In addition, there is a lower risk of viral contamination with cord blood than with bone marrow transplants.118 Whilst transplantation of HSCs from the umbilical cord blood of an HLA-matched sibling may present the best chance of recovery for

children suffering from some serious, life-threatening conditions, it is not without clinical limitations.

The statistical chance that a cycle of PGD will provide an HLA-matched embryo is relatively low, at only 25 per cent. This percentage falls to around 18 per cent if PGD is performed to diagnose an embryo that is both free of an autosomal recessive condition, such as Fanconi anaemia or thalassaemia, and is a suitable match.119

Transplantation of umbilical stem cells is currently limited by the age and weight of the affected child. Whilst cord blood may be adequate for small children below 25kg, bone marrow transplantation is usually indicated in the case of older children.120 In some instances this may preclude the performance of an umbilical transplant even after an HLA-identical sibling is born. Because of this, parents may seek subsequent bone marrow donation.121

Although an umbilical cord blood transplant lowers the risk of morbidity and mortality in the recipient, there is always a possibility that HSCT of umbilical cord blood will not be successful for several reasons. The transplant may be unsuccessful as a result of graft failure or because of a recurrence of disease in the sibling post transplant. Additionally, the success of the treatment may differ depending on the disease from which the sick child suffers.

It is established that disease-free survival (DFS) after HSCT with an HLA-identical donor is variable depending upon the disease suffered by the sick child.122 HSCT from a compatible donor does not guarantee the donee a disease-free existence; but, for certain diseases, it comes close. Whilst DFS is only 30 to 50 per cent for some acquired illnesses, such as acute leukaemia and non-Hodgkin lymphoma, it may be as high as 80 to 90 per cent in the case of acquired severe aplastic anaemia.123 DFS also appears to be relatively high in the case of genetic diseases such as thalassaemia major (70 to 90 per cent cure), sickle cell anaemia (80 to 90 per cent cure) and Fanconi anaemia (80 to 90 per cent cure), and in the case of immunodeficiencies (70 to 90 per cent cure).124

Possible risks to the future child have also been a limiting factor. Potential harms to a child born as a result of PGD with HLA tissue typing may arise not only as a result of the retrieval of cord blood stem cells, but as a result of the IVF cycle, or at the point of embryo biopsy. Currently, evidence indicates that the physical risk to a child born after embryo biopsy carried out in the course of PGD is not significantly greater than that incurred with IVF in general.125 The incidence, and nature, of

obstetric and neonatal complications after PGD is comparable to those reported after IVF alone.126

Although the risks involved with PGD are not significantly greater than those linked to IVF, there are established risks associated with IVF. Singleton children born as a result of IVF are more likely to be born early, be of low birth weight and have poorer neonatal health outcomes than naturally-conceived children.127 The risk of preterm delivery for singletons conceived as a result of IVF is around twice that of natural conception. Neonatal, perinatal and infant mortality rates are twice as high for babies conceived by IVF as for natural conceptions.128 Although these risks exist, they are not generally considered sufficiently high to deter infertile people from attempting to achieve a pregnancy, or legally to preclude them from doing so.

Generally, obtaining cord blood HSCs poses negligible physical risk to the neonate as the cells are aspirated from the umbilical cord and placenta after the umbilical cord has been clamped. However, it is possible that aggressive early cord clamping may have adverse effects on a premature newborn or a newborn of very low birth weight.129 Because the likelihood of successful transplantation of cord blood HSCs is related to the volume and cell dose collected, there is pressure to ensure a sufficiently large volume of cord blood at the time of collection.130 Early cord clamping as close to the neonate as possible ensures that the largest possible volume of neonatal blood is retained in the placenta and umbilical cord. However preterm babies are at risk of anaemia and haemodynamic instability. There is some evidence that a 30 to 120- second delay in umbilical cord clamping is associated with fewer transfusions for anaemia and fewer intra-ventricular haemorrhages in preterm infants.131

A little-mentioned fact is that certain diseases, such as insulin-dependent diabetes mellitus, multiple sclerosis and rheumatoid arthritis, have shown associations with certain HLA antigens.132 For example, ankylosing spondylitis is associated with the HLA B27. A person with B27 has a ‘markedly increased risk’ of developing the condition.133 When an embryo is HLA tissue typed, the procedure is carried out without determining if it is associated with a certain disease. However, it has been stated that the increased risk will be relatively small in most cases.134

It may be thought difficult to justify HLA tissue typing given the low prospects that an HLA-matched embryo will be created, and the even lower chance that an embryo at risk of inheriting a genetic disease will be both an HLA match and mutation- free. However, it may also be argued that the statistics are not so low as to make it unreasonable to attempt PGD with HLA tissue typing in the case of some severe or life-threatening diseases where cord blood HSC transplant confers a reasonable chance of success.

Because using PGD to conceive an HLA-matched child involves intensive technical intervention, it is inaccurate to describe the entire process as a minimal-risk procedure. The clinical risks involved are the generic risks associated with IVF, with additional potential risks in the case of a preterm or low birth weight neonate in relation to early cord clamping. What may be said is that the risks are those known risks associated with IVF, and the as yet unknown long-term effects of embryo biopsy. However, these clinical risks must be balanced against the disease-free survival rates of children after umbilical cord HSC transplant from HLA compatible siblings. These statistics are extremely compelling for certain disorders, and include disorders which are both genetic and non-genetic in origin.

However, it is clearly possible that a child conceived to be an HLA match for a sick sibling could face the prospect of donating bone marrow instead of umbilical cord blood; or could face subsequent bone marrow donation after an initial umbilical cord cell transplant fails. It is possible that chemotherapy and irradiation or immunosuppressive drugs, which must be undertaken by the donee prior to HSCT, may cause organ damage and subsequent organ failure in the recipient’s kidneys, liver or other organs.135 Hence there is potential for the recipient, at some point in the recipient’s life, to require tissue or even solid organs beyond that provided by the initial cord blood transplant, and the HLA-matched sibling will be a likely candidate as a donor.

Consequently, concerns are not limited to potential physical risks, but extend to possible psychological sequelae for a child that is conceived to be a donor. Justifications provided for restraint include the potential instrumentalisation of the future child, the possible physical exploitation of the donor child for ongoing donation and the concern that parents may feel morally obliged to engage in this technology if it becomes more prevalent. There are concerns that extending the ambit of PGD to selection on the basis of tissue type could lead to the use of foetal tissue to provide HSC, and the use of PGD for selection of non-medical traits.

Starting from a presumption of reproductive freedom, the critical issue is whether the concerns raised are sufficient to displace the interests of parents, who wish to undergo the procedure when there is a reasonable chance of success, and of the sick child, who may have an opportunity for survival. The principle of reproductive freedom and the primary purpose of the HART Act 2004, which is to ‘secure the benefits of assisted reproductive procedures ...’, must be borne in mind. Also relevant is section 4(a) which provides that the ‘health and well-being of children born’ should be an ‘important consideration’ in all decisions about that procedure. The Act also requires that the ‘health, safety and dignity of present and future generations should be preserved and promoted’.136 This clearly focuses attention not only on the child to be born, but also on the children already born to a family and the parents.

It will be argued that it is far more difficult to justify the restriction of this procedure than it is to defend its provision. Whilst it is accepted that there is a role for regulatory oversight by the State to protect the welfare of the donor child, the degree to which the State circumscribes access to this technology must be justified by reference to significantly relevant harms. Although there may be concerns that mandate caution, there are principles such as reproductive liberty and parental autonomy which point in a different direction.

Although there is an established legal regime which permits parents to provide proxy consent to sibling bone marrow donation on behalf of their incompetent minor children, most jurisdictions which permit PGD with HLA tissue typing require prior approval from the relevant body. New Zealand is no different. The reason for caution lies in the distinction between permitting an existing child to donate tissue, and creating a child for that purpose. However, the current guidelines narrowly restrict those who may access PGD with HLA tissue typing.

As previously indicated, HLA tissue typing is a regulated procedure under the HART Act 2004. PGD in conjunction with HLA tissue typing may only be carried out with prior ethical approval from ECART, the ethics committee established under the Act.137 ECART may only approve applications which are consistent with guidelines issued by ACART.138 The Guidelines are effective until 21 November 2007, unless revoked sooner.139

Section 2 of the Guidelines provides that HLA tissue typing in conjunction with PGD must be submitted for ethics committee approval on a case-by-case basis.140 The discretionary power of the ethics committee is significantly limited. The Guidelines provide specific criteria, which must be met in relation to both the affected child and the prospective embryo, before approval may be given. The final criterion requires that HLA tissue typing in conjunction with PGD may only be carried out where the health and well-being of the family/whānau has been fully considered. In relation to the existing sick child it is required that:

The restrictive nature of the Guidelines indicates an overriding concern to protect the perceived interests of the future child. Section 4(a) of the HART Act 2004 provides that ‘the health and well-being of children born as a result of the performance of an assisted reproductive procedure should be an important consideration in all decisions about that procedure’. However, it is not the only relevant principle in this context. A critique follows of arguments based on the health and well-being of the future child which have been put forward to justify the restricting of HLA tissue typing.

Those who are fundamentally opposed to HLA tissue typing in principle perceive that conceiving a child for the purposes of providing a donor sibling is an aberration of responsible parenthood.141 The concept of responsible parenthood in this context presumes two beliefs in particular: first, that ‘good parents conceive a child for itself ’; and, secondly, that ‘good parents accept the child as it comes’.142 This latter view which demands nothing less than unconditional acceptance of a prospective child is problematic under existing law. It would preclude the conception of a saviour sibling when the sick sibling suffers from a genetic disorder – a process already permitted under the current Guidelines. If carried to its logical conclusion, it would also preclude prenatal testing and abortion as well as selection on the basis of any disability whatsoever, and this would be incongruent with the law. Consequently, this is not a tenable argument to justify legal restriction.

It has been argued that intentionally conceiving an HLA-matched child to act as a donor instrumentalises and treats the prospective child as a means to an end, rather than as an end in its own right. This constitutes a prima facie breach of that future child’s inherent dignity and breaches the Kantian dictum to “Act so that you treat humanity, whether in your own person or in that of another, always as an end and never as a means only”.143 However, it is trite to counter this perceived ethical breach by distinguishing between using a person as a means to an end and solely using a person as a means to an end.144 Whilst the former is a part of every day life, the latter is objectionable.

The idea that parental motives for having a child must not be superimposed with any collateral parental goals is an idealistic concept. The reasons why parents choose to conceive children are numerous and varied, and some undoubtedly nobler than others. Conception may occur as a result of a couple’s combined desire to raise and love a child, or to appease a partner who wants a child, or to provide a playmate for an existing child, or to attempt to have a child of a particular sex. Concerns of

instrumentalisation are not persuasive when it is considered that conceiving a child to be a donor ‘is not any worse or less altruistic than the myriad of other reasons for which children are sought’.145 The morally relevant point is that the parents want the child in the child’s own right.

It has been observed that concerns that a saviour sibling were regarded solely as a means to an end would be borne out if the parents abused or neglected the donor child, or surrendered the child for adoption after cord donation.146 Some ethics committees have considered that the absence of a prior wish to conceive a child before the need to create a donor arose may be prima facie evidence of instrumentalisation of the prospective child.147 This could constitute criteria for denying parents the opportunity to conceive a saviour sibling. Yet this ‘prior wish’ concern is not persuasive. It is not uncommon for people to change their reproductive plans given a change in parental attitudes or personal circumstances. What is important is that the prospective child is wanted as well as being able to be a compatible tissue donor. The motives parents have for conceiving a child are not decisive of the relationship they will have with that child. Rather:

The morally relevant point is not that parents have the right motive for conceiving the child, but that they love and care for the donating child and protect its best interests once it is born. The few instances in which parents have asked for medical assistance to obtain a compatible sibling strongly indicate that they intend to do so. The use or instrumentalization of the donating child does not demonstrate disrespect for his or her autonomy and intrinsic value.148

The basis for concerns regarding instrumentalisation is that the procedure is not carried out for the benefit or best interests of the child born, but to benefit a third party. However, it has been cogently argued that psychosocial benefits may accrue to a donor child as a result of being a donor.149 These benefits are that the child is born into a family which has a chance of remaining intact. The child has the benefit of growing up with the sibling if the HSCT is successful. Essentially, the benefit is that which accrues to the entire family in the event that the sick child is cured.150

Although embryo biopsy does not appear significantly to increase the risks associated with IVF, the long-term effect of PGD will not be known until sufficient empirical studies establish good scientific data. This uncertainty must be balanced against the potential benefit to the sick sibling and the family.

It will be argued that the limitations imposed both in relation to the sick child and the prospective embryo, except for the requirement that the embryo be a sibling of the affected child, are clinically, ethically and legally problematic. Taken together, these difficulties mandate wholesale revision of the HLA guidelines.

The affected child suffers from a familial single gene disorder or a familial sex- linked disorder

The objective of clause 7.1 is to restrict the performance of HLA tissue typing to circumstances in which the sick child is suffering from a disorder which is genetic in origin.151 However, the effect of drawing a distinction between genetic and non- genetic conditions can have capricious results. The restriction means that the parents of a child who is suffering from a serious, life-threatening condition cannot attempt to access this procedure if their child’s illness is not heritable. Some conditions such as diamond black fan anaemia (DBA) may be the result of either a sporadic or an inherited mutation. DBA is a rare form of anaemia which results in bone marrow failure. Although DBA may initially be treated with steroids, the only cure is HSC transplantation. Under the current guidelines, parents whose child is suffering from inherited DBA may apply to undergo PGD with HLA tissue typing, whilst those whose child has a sporadic mutation may not.

The restriction in clause 7.1 is based on concerns for the putative donor child. Whilst the consequences of being conceived to be a donor child must be addressed under the Act, the balance of argument weighs against restricting HLA tissue typing to instances where there is a genetic risk. This very issue was played out in the United Kingdom when the interim HLA tissue typing policy of the Human Fertilisation and Embryology Authority (HFEA) was released in 2001.152 It was the first attempt to delineate parameters permitting the creation of saviour siblings utilising PGD technology.153 The current New Zealand policy on HLA tissue typing bears a striking resemblance to this initial HFEA policy.

Under the Human Fertilisation and Embryology Act 1990 (UK), the HFEA, when drafting policy, is similarly required to take account of the welfare of any child born as a result of treatment.154 Significantly, the HFEA received advice provided by the HFEA Ethics Committee that, when considering the welfare of the unborn child, the inquiry should not be restricted to a narrow, legal perspective regarding the future child’s welfare or best interests.155 Rather, it should include the ‘wider question of the putative child’s moral, psychological, social and physical welfare’.156 The Ethics Committee favoured a principle of ‘constrained parental decision-making’ with regard to performing PGD with HLA tissue typing.157 It was recommended that the technique should be available where an existing sibling suffered from a life- threatening but non-genetic condition.

These recommendations were not followed by the HFEA. The interim HFEA policy authorised the performance of HLA tissue typing in conjunction with PGD, but

restricted the procedure, as under the current New Zealand guidelines, to instances where the condition suffered by the sick sibling was genetic in origin. The rationale for this distinction was the purported lack of evidence regarding future health risks to the resulting child from the embryo biopsy. Consequently, embryo biopsy could only be considered to be in the interests of the future child if it conferred the primary benefit of being born free of a genetic disorder. Where the putative risks of biopsy could not be justified on the basis of this perceived benefit to the future child, then carrying out the procedure could not be justified, as it would not be in the interests of the future child.

The distinction made by the HFEA has been the subject of sustained academic criticism.158 One criticism made is that it is inaccurate to describe embryo biopsy as conferring the benefit of a disease-free existence on the resulting child where there is a risk of inheriting a genetic disorder. Biopsy merely detects the presence or absence of a genetic mutation; it does not change disease status.159 Ultimately, biopsy confers the benefit of provision of information on which the decision to select the embryo for transfer is made. The benefit comes down to selection for implantation. Consequently, the distinction between performing biopsy in the presence or absence of genetic risk on the basis that it confers a benefit on the resulting child in the former case but not in the latter is erroneous.

The restrictive interim HFEA policy was put to the test when the first family with a child suffering from a disorder which was not genetic in origin applied, unsuccessfully, for approval to undertake PGD in conjunction with HLA tissue typing.160 The case received widespread media and academic attention.161 Ultimately the HFEA’s restrictive policy could not be retained in the face of the compelling arguments raised.

In 2004 the HFEA released a new policy on preimplantation tissue typing, which dispensed with the distinction between performing HLA tissue typing in the presence or absence of genetic disease. Effectively, the original recommendations made by the Ethics Committee in 2001 were adopted in the revised policy.162 It was stated that:

Balancing the likely benefit of preimplantation tissue typing – to the sick sibling, the new baby and the family as a whole – against a better understanding of the possible physical and psychological risks to the child to be born, the Authority concluded that preimplantation tissue typing should be available, subject to appropriate safeguards, in cases in which there is a genuine need for potentially life-saving tissue and a likelihood of therapeutic benefit for an affected child.163

For similar reasons, the current restrictive policy in New Zealand should be rejected.

The restriction contained in clause 7.1, that the sick child must be suffering from a familial single gene or sex-linked disorder, is not only unjustified, it is reductio ad absurdum when clause 7.5 is taken into consideration. The criteria set out in the Guidelines are cumulative; hence, all of the criteria specified must be present before approval may be given by ECART. Clause 7.5 permits HLA tissue typing when, in addition to the other requirements, the embryo is at risk of being affected by a familial single gene disorder or a familial sex-linked disorder for which a PGD test is available. Consequently, if a prospective child is at risk of inheriting a disorder such as cystic fibrosis, and an existing sibling is suffering from a non-heritable condition which could be cured by HSCT, HLA tissue typing may not be performed because the life-threatening condition of the sick sibling is not genetic in origin as required by clause 7.1. This is the case even though PGD to diagnose cystic fibrosis may be performed as an established procedure.

There is a remote possibility that parents with a healthy child may want to undergo PGD with HLA tissue typing to conceive an HLA-compatible sibling, in the absence of any disorder, to create a family in which the children could serve as mutual donors if ever necessary. In this context there is ‘reciprocity of opportunity and obligation, unlike the situation in which the first-born was already ill’.164 What if such couples are sufficiently wealthy to pay for treatment and are willing to accept the risks involved with the procedure?

At least one commentator is of the view that, based on considerations regarding the risks of PGD and the welfare of the donor, we have no good reason to object as ‘we already accept the risks of PGD in order to benefit people with the desire for a child, and the child will certainly be created for its own sake, since its use as a donor is only conditional’.165 Yet there seems to be a relevant distinction to be made in the case where there is no threat to the life of a sibling. Relevant factors include the risks associated with IVF babies which may utilise additional public resources. Aggressive ovarian hyperstimulation regimes will potentially be required, so that there are sufficient ova to be fertilised from which to obtain a match, which confers health risks for the woman involved.166 It would also be harder to maintain arguments relating to ‘designer babies’ and ‘slippery slopes’ in this context.

Conversely, selection on the basis of HLA compatibility could be construed as falling within the domain of preventative medicine and, on these grounds, could be argued to be acceptable. Yet the chances of children needing an HSC or solid organ transplant in their lifetime are not high unless they have a particular genetic history. Additionally, there is no positive right to treatment. A fertility services provider is at liberty to decline to provide a procedure.167 Because of this, performing the procedure in these circumstances has a low value, apart from gratifying parental preferences, and less justification is required for restricting such an endeavour.

The current prohibition of HLA tissue typing in the absence of a heritable disorder is not morally or legally justifiable on the grounds of lack of benefit to the future child. The benefits which derive from HLA tissue typing are selection itself, which is the same whether there is the risk of transmitting a genetic disorder or not, and the potential benefits which may accrue to the family as a whole. In the absence of empirical evidence indicating that embryo biopsy is harmful to the prospective child, public policy which precludes a therapy by which a sibling’s life may be preserved is exceedingly difficult to justify and appears to make an arbitrary distinction.

PGD with HLA tissue typing and HSC transplant should only be considered when the sick sibling has a disorder which is serious or life threatening and there is a reasonable chance that HSC transplant will be successful. This acknowledges the concerns in relation to the donor child. In this context, ‘serious’ should be interpreted as sufficiently serious to justify the clinical risks to the recipient in undergoing the transplant. These risks include the treatment regime prior to transplant, which may involve ablative chemotherapy and total body irradiation ‘to destroy disease and prevent the rejection of donor cells’, and the post-operative risks such as graft-versus- host disease, infection and relapse.168

Clause 7.2 restricts HLA tissue typing to circumstances where there are no other possibilities for treatment or sources of tissue available. It suggests that all other avenues for treatment must be exhausted before considering the conception of an HLA-matched sibling with the aid of PGD, effectively making it a last-resort therapy. The high threshold is not problematic in instances where there is no alternative effective clinical course available, such as in the case of Fanconi anaemia.169 However, other diseases may not be as straightforward.

The provision which requires that HSCT should not be performed where there is an alternative treatment available is prima facie defensible. Many children with serious stem cell defects can be successfully treated without HSC transplantation.170 For example, bone marrow transplantation for childhood acute leukaemias, such as acute lymphoid leukaemia (ALL) and acute myeloid leukaemia (AML), may not necessarily be required because treatment with chemotherapy alone has an 80 per cent five-year cure rate in children with ALL and 60 per cent in children with AML.171 Stem cell transplant for children with a first remission is ‘generally considered only for those at high risk’, as results for transplantation are claimed to be less successful than those for chemotherapy alone.172

However, some sick children who are not in immediate need of a transplant may require transplant in the future if their current therapy fails.173 Waiting until a child relapses before initiating PGD may mean that the mother has lost valuable reproductive time, or that the child may deteriorate in the time taken to conceive an HLA-matched sibling. Performing PGD solely to obtain a backup or possible donor may seem disproportionate in terms of the technical expertise, personnel and cost involved.174 Conversely, a pathological condition exists which, although in remission, has a statistical chance of recurring. On balance, it seems difficult to justify prohibiting this option when parents desire another child.

The HFEA considered this issue when it undertook the review of preimplantation tissue typing policy in 2004. It found that there was ‘no objection in principle’ to applications for HLA tissue typing being considered in the same way both in cases when the existing child is not symptomatic but is in remission and when the affected child is symptomatic at the time of the application.175 This is a flexible approach, which is still guided by the underlying medical condition of the sick child and the clinical context.

The current provision that PGD with HLA tissue typing may only be performed when no other possible treatments or sources of tissue are available is unduly onerous. Tissue typing should be permitted when HSC transplant from an HLA- matched sibling constitutes the best clinical option after all other possibilities for treatment for the affected child have been explored. However if the parents wish to have a subsequent child, their application to perform HLA tissue typing should also be considered because of the risk of relapse, even if the affected child has undergone successful alternative treatment.

The planned treatment for the affected child will utilise only the cord blood of the donor child

Clause 7.3 imposes a limit on the extent to which a donor child may provide tissue for a sibling. The intuitive fear that an HLA-matched child may be used as spare parts is not easily dismissed. Ethicists and experts alike have voiced concerns regarding the potential exploitation of the vulnerable neonates and the children they develop into.176 Such concerns are articulated in the following:

The donor child is at lifelong risk of exploitation, of being told that he or she exists as an insurance policy and tissue source for the sibling, of being repeatedly subjected to testing and harvesting procedures, of being used this way no matter how severe the psychological and physical burden, and of being pressured,

manipulated, or even forced over protest. The parents must intend to rear the donor child lovingly with that child’s individual best interests governing all medical decisions for the child.177

However, clause 7.3 is problematic both procedurally and substantively. Guidelines promulgated pursuant to the HART Act 2004 may legitimately regulate assisted reproductive procedures. Conversely, procedures which do not constitute an assisted reproductive procedure, such as sibling bone marrow transplant undertaken after the birth of a child or, for that matter, the donation of cord blood postnatally, are not within the scope of the policy-making authority conferred under the Act. However, the purpose of HLA tissue typing is relevant to procedures performed under the HART Act 2004. The relevant purpose of HLA tissue typing is to determine whether a prospective child is a tissue match for a seriously ill sibling and could act as a tissue donor. But restricting procedures performed after birth is outside the scope of the authority conferred on ACART or ECART by the Act. Clause 7.3 seems to be ultra vires the Act.178 Setting aside the vires issue, the question is whether it is appropriate to limit to cord blood only the future donation by the HLA-matched child. It is argued that such a restriction is not justified and is not consistent with existing law and practice in relation to naturally conceived children.

Because of these legitimate concerns regarding exploitation, it is impossible to address in isolation the issue of the creation of children who are compatible tissue matches and cord blood donors for seriously ill siblings. The enduring concern that a saviour sibling may be an ongoing source of tissue for a sick child means that this analysis necessarily requires a review of the ethics and law in respect of the donation of tissue and organs by an incompetent minor to a sick sibling. It is necessary to consider the donation of both regenerative and non-regenerative tissue by incompetent children to siblings. This analysis focuses on whether, as a matter of law, babies born as saviour siblings may provide bone marrow or non-regenerative organs to sick siblings.

It is worth noting at the outset of this section a submission NECAHR (the body responsible for drafting the Guidelines on Preimplantation Genetic Diagnosis) received from the Health and Disability Commission when it undertook the public consultation on the Guidelines. The Health and Disability Commission is required under the Health and Disability Commissioner (HDC) Act 1994 to make public statements in relation to any matter affecting the rights of health and disability services consumers, and consequently provided a submission on the Guidelines.179

Whilst it appeared to accept that creating an HLA-compatible child was justifiable in some circumstances, based on the medical health of the family, strong support was given in the submission for restraining the future donation of tissue from the donor child. The submission opined that the regulatory body should

predicate its approval [for PGD in conjunction with HLA tissue typing] upon assurance from the family and the clinic that only cord blood (and not other tissues or organs) of the new child will be used to treat the ill sibling.180

It was stated in the submission, uncontroversially, that the HDC Act 1994 and the Code of Health and Disability Services Consumers’ Rights apply to children resulting from PGD.181 Although not a person for the purposes of the Act or the Code at the time PGD is performed, the child born as a result of PGD is a health consumer as defined in the HDC Act 1994. Right 2 of the Code confers on health consumers the right to be free from discrimination, coercion, harassment and exploitation, and right 3 confers the right to dignity and independence. It was claimed that, taken together, rights 2 and 3 would prohibit the subjection of a patient below the age of consent to surgery for the benefit of another. This aspect of the submission is open to the challenge that the legal basis for the recommended restraint is questionable.

There are no specific legislative provisions governing children acting as tissue or organ donors for siblings in New Zealand, nor has this issue come before the Courts.182 However, section 16(1) of the Care of Children (CoC) Act 2004 provides that ‘the duties, powers, rights, and responsibilities of a guardian of a child include (without limitation) the guardian’s – (a) having the role of providing day-to-day care for the child ... ; and (b) contributing to the child’s intellectual, emotional, physical, social, cultural, and other personal development; and (c) determining for or with the child, or helping the child to determine, questions about important matters affecting the child’. ‘Important matters affecting the child’ include medical treatment for the child (if that medical treatment is not routine in nature).183 Consequently, guardians have the power to determine important matters affecting the child; and, specifically, they have the right and responsibility to determine questions regarding non-routine medical treatment.

Section 36(3)(a) of the CoC Act 2004 provides that, where consent to any medical, surgical, or dental treatment or procedure is necessary or sufficient, consent may be given by a guardian. The parental right to make decisions regarding medical treatment or procedures has long been part of the common law, but it is not absolute.184 However, the scope of parental power, and the point at which a Court will find that a decision is beyond the ambit of parental authority, differs between jurisdictions.185

It seems that the provision of proxy consent for bone marrow donation by an incompetent minor to a sibling has been viewed as coming within the scope of ordinary parental decision-making authority since sibling bone marrow transplants were first performed in New Zealand. The same has been true in some other jurisdictions, such as the United Kingdom; however this has changed to a certain extent with the introduction of the English Human Tissue (HT) Act 2004.

The HT Act 2004 came into force in September 2006. Under the Act, the Human Tissue Authority (HTA) is responsible for approving the transplantation of solid organs, bone marrow and peripheral blood stem cells from living donors.186 The HTA has statutory authority to issue Codes of Practice to provide guidance and standards for persons performing functions within its remit.187 Such a Code has been released with regard to the donation of allogeneic bone marrow and peripheral blood stem cells (PBSC) for transplantation.188 It has introduced new safeguards for incompetent minors. Whilst a guardian may provide consent for an incompetent minor, bone marrow donation may only be performed if the HTA and an accredited assessor are satisfied that the best interests of the child have been properly considered and the HTA’s code of practice has been properly implemented.189 The assessor is responsible for interviewing the child and guardian, and acts as an advocate for the child. Following this a report must be submitted to the HTA stating that the assessor is satisfied that:

of the registered medical practitioner and their qualification to give this information;

The report is valid for six months. Whilst there is no criminal sanction for breaching the Code of Practice, any breach may be taken into account in decisions regarding licensing. If the transplant does not occur within the six months, another report must be undertaken.

In Australia, the donation of regenerative tissue such as bone marrow by a minor to an immediate family member is generally covered by statutory provisions, and the requirements vary amongst the different States and Territories.191

In New Zealand, bone marrow donation by an incompetent minor is not specifically regulated, but is governed by the general law regarding consent for medical procedures on incompetent minors, i.e. the CoC Act 2004, the common law and the Code of Consumers’ Rights. Right 7(1) of the Code of Consumers’ Rights provides that ‘services may be provided to a consumer only if that consumer makes an informed choice and gives informed consent, except where any enactment, or the common law, or any other provision of this Code provides otherwise. Clause 4 of the Code provides that, for the purposes of right 7(1), ‘consumer’ includes a person entitled to give consent on behalf of that consumer, which encompasses parents who are legally entitled to provide proxy consent for health care procedures performed on their minor children.

Clearly, the Code does not alter the position at law, and guardians may provide proxy consent for incompetent minors. The Health and Disability Commission submission appears to have been based on an assumption that the donation of bone marrow by an incompetent minor to a sick sibling was exploitative, a breach of the dignity of the donor child and not capable of being consented to by a guardian. It is significant that the Council of Europe’s Convention on Human Rights and Biomedicine countenances the donation of regenerative tissue by a minor to a sibling suffering a life-threatening condition where there is no other competent available donor.192

It is argued that the Health and Disability Commission submission was flawed and does not represent the legal position in New Zealand. There is, as yet, no judicial or

legislative statement that providing proxy consent to sibling bone marrow donation is beyond the scope of parental authority. However, parental consent to a medical procedure on a minor can be challenged by any eligible person under the CoC Act 2004.193 If donation is not in the best interests of the child, the Court has powers under the CoC Act 2004 to place the child under the guardianship of the Court and to appoint an agent of the Court.194 Alternatively, an application may be made to the Family or District Courts under the Children, Young Persons, and Their Families Act 1989 for a declaration that a child is in need of care and protection.195 The Court may then make a guardianship order.196

This report now examines the common law basis for provision of proxy consent by parents for the donation of tissue by an incompetent minor to a sibling in relation to both regenerative and non-regenerative tissue. It considers at the outset the risks of bone marrow donation to the donor child. Finally, the question of whether a distinction should be made between donation of tissue by neonates and donation by older children will be addressed.

Prior to bone marrow donation, pre-harvest screening tests must be undertaken to determine whether a child is HLA compatible with the sick sibling. In the case of HLA compatibility, bone marrow aspiration is performed under general anaesthesia. Because anaesthesia is required, bone marrow donation poses more than a minimal physical risk to a donor child. This risk is heightened to an extent if a blood transfusion is required as part of the procedure.

Pain and fatigue are the most common symptoms described by donors after donation of bone marrow. However, bone marrow regenerates in approximately three weeks. It is reported that minor complications occur in between 6 per cent to 20 per cent of bone marrow donations, with serious complications in 0.1 per cent to 0.3 per cent.197 In the case of paediatric donation serious complications are rare, but children are more likely than adults to receive a blood transfusion.198

One small study which looked at the psychosocial impact of bone marrow donation by siblings cautiously indicated that the psychological effect on a bone marrow donor is significantly affected by whether the HSCT is successful or not.199 Whilst almost all sibling donors who participated in a successful HSCT believed that the donation had had a mostly positive impact on their lives, this theme emerged to a much smaller extent with those siblings who participated in an unsuccessful transplant. Siblings often felt responsible for the death of their sibling when the transplant was unsuccessful. All donors reported that the psychological burden of being a donor was greater than the physical aspect of undergoing the procedure. The study highlighted

the importance of providing children with developmentally appropriate, accurate information and psychological support.200 Another study, which looked at the psychosocial impact on siblings of children who underwent successful bone marrow transplant, found symptoms of post-traumatic stress in both donor and nondonor siblings.201 The study emphasised the need for ongoing research and support for both donor and nondonor siblings.

It has been argued that, when balancing the harms and benefits involved in sibling bone marrow donation, if the ‘minimal risks affecting the donor are compensated, according to a reasonable prediction, by significant potential benefits for the recipient- patient’ ... then compliance with the ethical principle of nonmaleficence is achieved.202 Consequently, paediatric bone marrow transplantation ‘has been confirmed as an ethical practice, because its benefits abundantly prevail over its costs and risks’.203 However, if the physical risk to the donor of bone marrow is substantially greater than minimal, harvesting should not be permitted unless that risk may be ameliorated.

It has traditionally been argued that parental consent to sibling bone marrow donation may be justified on the grounds that it is in the best interests of the child to donate.204 (However, it should be noted that section 36 of the CoC Act 2004, which authorises proxy consent by a guardian when such consent is necessary and sufficient, does not specify best interests.)

There is increasing criticism of the use of the best interests standard in the context of sibling donation. It seems to be widely perceived as inaccurate to view a procedure which poses some risks and confers no physical therapeutic benefit to be in the best interests of the donor child. However, a broad approach to the best interests test may be applied. Such an approach has been adopted by the High Court in the United Kingdom, authorising the performance of blood tests and bone marrow harvesting on a mentally incapacitated adult for the benefit of her sister. It was held that the best interests standard included both physical and psychosocial interests.205 Similarly, a wider construction of the best interests standard arguably includes the ‘benefits the child receives when he or she makes a contribution to the welfare of another person to whom he or she stands in an intimate relationship’.206 In an Australian case it was held that consent to bone marrow donation by a nine-year-old boy for the benefit of his aunt would be beyond the ordinary scope of parental decision-making. In this particular case it was held to be in his best interests because the boy firmly wished to be a donor and had a close relationship with his extended family, and the risks were small.207 An alternative means of justifying proxy parental consent for sibling bone marrow donation is where a procedure is ‘not against the interests’ of the child.208

Some commentators have argued that bone marrow donation by minors to siblings should be regulated and parents should be required to apply to a specialised national or regional ethics committee to ensure that donation is not against the interests of the donor.209 Others believe strongly that legislating is not the appropriate response in order to protect the interests of children in this context.210 Rather, parents should be made fully cognisant of what is entailed in bone marrow donation for both donor and donee, and be motivated to consider the interests of both children.211

As already indicated, bone marrow donation is not specifically regulated at present, and parents may provide proxy consent under the general law governing incompetent minors. However, it should be acknowledged that it is not only the donor child’s interests which must be considered in this context. A highly relevant clinical question is whether the parents are acting in the best interests of the sick child, as well as in the best interests of the donor child. This is apparent in the following statement by a clinical paediatric oncologist:

... I think a far more compelling issue [than that of putting more constraints on bone marrow donations by siblings] is whether a parent is acting in the best interest of the ill child who is the potential recipient. Often parentsbelieve a bone marrow transplant is the only hope and are compelled to try it even when the evidence for success is slim.

Sometimes paediatric bone marrow recipients suffer immensely because of the side effects and complications of a transplantthat has almost no chance of success. There could usefully be far more scrutiny of the process by which parents make the decision for their child to undergo bone marrow transplantation.212

One factor, identified as an important consideration affecting the decision-making of parents of seriously ill children, has been described as ‘anticipated decision regret’.213 Parents need to know that they have done everything possible to save a child, so as not to blame themselves later. Some parents may consider that conceiving a saviour sibling to provide cord blood or bone marrow is both a parental and medical imperative. Parents may be driven to pursue this. Depending on the clinical circumstances, however, bone marrow transplant may not be the best course of action.214 Ultimately, a provider may not be compelled by parents to provide treatment which is clinically inappropriate and contrary to good medical practice.215 When the situation is not as clear-cut as this, the matter may need to be resolved in Court.216

The law currently confers significant latitude on parents to provide proxy consent for a child to donate regenerative tissue for a sick sibling. A major factor in this is the assumption that parents will sometimes be justified in making decisions which affect individuals in a family differently, but which are required to further the interests of the entire family.217 However, such latitude is only permissible when the harm is

considered to be de minimis and there are contingent benefits to the donor.218 Clearly clinicians as well as parents are justified in refusing donation when it is perceived that the harms of the procedure are not mitigated by any putative benefits.219 The Code of Consumers’ Rights should not be interpreted as precluding parents from providing proxy consent for bone marrow donation by an incompetent minor to a sibling with a life-threatening illness. However, each case should be judged on its own facts and the clinical circumstances.

In a survey reported in 1996, seven out of fifty-six North American paediatric transplantation centres reported that they would not collect bone marrow from infant donors under six months old.220 However, most would be prepared to harvest marrow from infant donors over the age of six months. Although serious complications are rare in the case of paediatric donors, a 1987 study revealed that donor children under the age of two are likely to receive blood transfusion.221

It has been argued that neonatal donation of umbilical cord blood (which imposes virtually no physical risk) should be distinguished from neonates acting as bone marrow donors for a sick sibling. This argument is predicated on both psychological and physical grounds. It is claimed that the lack of a close relationship with a sibling precludes a presumption of psychological benefit to the neonate donor. Because of this, a neonate should not serve as bone marrow donor for a sick sibling.222 Donation would have to wait until a sufficiently close relationship developed between the siblings, regardless of whether this was too late.

This claim seems hard to sustain. Generally, it is perceived to be a benefit to have a healthy sibling to grow up with. At the very least, an ordinary sibling relationship may be assumed if the sick sibling survives. Additionally, it is likely that the saviour child will have a happier family life living in an intact family rather than one marred by the effects of a sibling’s premature and potentially avoidable death. In addition, in the event that the transplant were not successful it would be extremely unlikely that the neonate or infant would have any recollection of the events which had taken place.

Bone marrow donation by an HLA-matched child conceived with the aid of PGD is governed by the CoC Act 2004, the common law and the Code of Consumers’ Rights. Donation of bone marrow places significantly greater physical burdens on a neonate

Clinical considerations will be highly relevant in determining whether the procedure is in the best interests of the child when the donor child is a neonate. However, the procedure may be in the best interests of the child as understood in the wider sense of the term or at least may not be contrary to the child’s interests. In that case parents

may provide proxy consent to bone marrow donation by a child regardless of the child’s age. If, on the other hand, the procedure is contrary to the child’s interests, the parents’ consent is open to legal challenge.

A much more difficult issue in the context of children conceived to be donors is the donation and transplant of non-regenerative organs, such as kidneys. Whilst there have been no reported cases of incompetent minors acting as kidney donors in New Zealand and Australia, this appears to be a result of clinical practice, rather than formal policy.223

The British Medical Association considers that it is inappropriate for incompetent minors to donate non-regenerative tissue or organs.224 In contrast, professional guidelines in the United States endorse living kidney donation by minors but provide strict criteria.225 In Hart v Brown226 a United States Court allowed a seven- year-old girl to donate a kidney for her identical twin sister.227 In Australia, the only jurisdiction that expressly permits donation of non-regenerative tissue from minors is the Australian Capital Territory.228 The removal of non-regenerative tissue from minors is expressly prohibited in Victoria, South Australia and Western Australia and is arguably prohibited by implication in the three remaining Australian States.229

Although it has been argued that it is not within the mandate of ACART to determine parameters regarding donation of tissue by a child conceived by PGD with HLA tissue typing after birth, it is impossible to consider the merits of allowing PGD with HLA tissue typing in isolation from the possible long-term sequelae. This was expressly acknowledged by the HFEA when revising the guidance on preimplantation tissue typing:

The HFEA does not have the power to impose a condition on a license that would prohibit any future attempt to obtain bone marrow, should a cord blood donation fail. However, the Authority noted that obtaining bone marrow for the treatment of siblings from children from the age of one year was a relatively routine treatment strategy where no other matched donor was available. The Authority also noted that, under common law, the best interests test applied by the courts when considering the type of medical procedures that may be performed on a child, is very much higher when such treatment gives no health benefit to the child concerned. As such, solid organ donation is extremely unlikely to be held to be in a child’s best interest. Having considered typical arrangements for decision making with respect to child bone marrow donors, the Authority found that existing arrangements were sufficient to protect the welfare of the child in these circumstances.230

Because there is ethical scrutiny, by virtue of the Guidelines, of parents wishing to conceive an HLA-matched child in New Zealand, external ethical oversight is imposed which does not occur with sibling bone marrow donation. Whilst some may advocate similar ethical approval of bone marrow donation, these decisions have been made by parents and clinicians for many years without incident. Whilst there may seem little reason to introduce such regulatory oversight, in the light of scientific advances, which mean that children may be born because of their HLA tissue type, it may be timely to consider additional safeguards.

Concerns regarding exploitation are valid but may be accommodated by standards of clinical practice, and are not sufficient on their own to justify restricting the performance of HLA tissue typing. Good medical practice should dictate that, if a cord blood HSCT fails, then HSC transplant using bone marrow is an acceptable clinical course, depending on the clinical circumstances of the affected sibling and the HLA-matched infant. It would seem inhumane to permit a couple to conceive an HLA-matched child, only to draw an arbitrary line regarding donation once the child is born. It is also inconsistent with current practice regarding sibling bone marrow donation.

If such a transplant fails, subsequent donation should be a matter of clinical and parental judgment. Ideally an appropriately qualified independent advocate should be appointed on the donor child’s behalf, as well as a physician who is not responsible for the treatment of the affected sibling.

Clause 7.4 limits the potential recipients of umbilical cord blood in the case of an intentional HLA tissue match to a sibling.231 However, the question of whether PGD in conjunction could or should be performed for the benefit of others, in particular a parent, has been raised.

The possibility of conceiving a tissue-matched child to benefit a parent in need of an HSC transplant has been raised following reports from the Netherlands that a man suffering from leukaemia was a recipient of a successful HSC transplant using the cord blood of his infant daughter.232 (A woman who is suffering from a disorder which necessitates HSC transplant is unlikely to be sufficiently robust to undergo PGD to create an HLA-matched child. Consequently it is assumed that the majority of these cases, of which there would not be many, would involve an illness suffered by the prospective father.) In addition to ethical concerns regarding the creation of

an HLA-matched child for the benefit of a parent, there is doubt whether such a procedure is clinically advantageous.

The small cell dose of HSCs derived from umbilical cord blood has been a major limitation in the use of cord blood for allogeneic transplantation in adults.233 The transplanted cell dose procured from umbilical cord blood is approximately 10 per cent of that obtained from bone marrow transplant, so has usually been limited to the treatment of small children.234 Regardless of this, transplantation of umbilical cord blood from unrelated donors into adults has been performed worldwide.235 Currently research is being undertaken into ex vivo expansion of umbilical cord blood stem cells to increase the cell dose.236

Although cord blood transplant into unrelated adults is occurring internationally, the chances of creating a child who is an HLA match for a parent are extremely low. The HLA genes are located in three clusters on chromosome six; each child has two copies of chromosome six, one inherited from the father and one from the mother.237 The three HLA gene clusters on each parental chromosome contain multiple HLA genes with many individual variants. The HLA markers present on a child’s leukocytes are a complex mix of HLA antigens inherited equally from each parent. Since the child inherits half of the HLA antigens (haplotype) from one parent and half from the other parent, a child will only match half of each parent’s tissue type exactly (a haplotype mismatch, or a half match). However, in some very rare instances a child can be matched with a parent.

Because a parent–child match would only be a partial as opposed to a complete match, it has been observed that a partial tissue match for the benefit of a parent would be ‘more practically achieved by searching existing donor registers than by selecting a tissue-matched embryo’.238 However, a complicating factor is that New Zealand does not have a public umbilical cord blood bank and adult patients with relatively unique mixed ancestry are sometimes impossible to match on the NZ Bone Marrow Donor Register, or on Bone Marrow Donors Worldwide.239 There is increasing evidence that ‘well collected and stored cord blood units’ can provide sufficient HSCs for transplanting adult patients in some instances.240 Because of this, it has been observed that it may be appropriate to revisit the arguments in favour of establishing a non-profit, public cord blood bank for the altruistic gifting of cord blood ‘specifically to meet New Zealand’s unique ethnic needs’.241 Significantly, a greater HLA mismatch is tolerated by the recipient when umbilical cord blood is used than is tolerated with bone marrow.242 Because of this tolerance for HLA incompatibility, it has been recommended that a ‘matched’ cord unit constitute a ‘4-of-6’ match.243 It is likely that the example from the Netherlands involved a partial match in the absence of an unrelated matched donor.

Ethical concerns regarding the creation of a donor child for the benefit of a parent have been based on the conflict of interest which may arise when a parent, who is also the proxy decision-maker for the putative child, is a potential recipient of the child’s umbilical cord blood. Welfare concerns include the possibility that the child may be born into a family which suffers the bereavement of a parent if the transplant is unsuccessful, or that the parent–child relationship will be distorted. Yet it is not generally suggested that parents with severe chronic illness, or potentially terminal illness, should not conceive children naturally. Rather, it is a matter of personal conscience. Some parents have gone to considerable lengths to conceive a child even after the death of a spouse.244 It could also be argued that the putative child’s interests may be affected more by the health status of a parent than is the case with a sibling. However, it has been observed that:

A parent who intends to have a child to save his or her own life cannot expect much goodwill from the social environment. Our moral intuitions condemn these applications, because of the considerable self-interest of the decision maker. The parent should declare him or herself incompetent due to a conflict of interest. Nevertheless, the same justification can be offered as for the donation to a sibling. The HLA-matched child will be better off, since it will have two healthy parents, while its incompatible possible sibling will experience parental death or will grow up in a family with a chronically ill parent. The conception of a child as a donor for a parent would also be acceptable according to the postnatal test: if an existing child in the family would be a suitable donor, it would be judged acceptable to use it as a donor of haematopoietic stem cells for a parent.However, we should take our moral intuitions into account by appointing an independent guardian who should, even more than in other cases, carefully scrutinise parental decision making.245

Six years ago Dr Paul Serhal of University College Hospital, London announced his intention to perform PGD with HLA typing for thalassemia, where the umbilical cord HSCs of the child could help cure the father.246 However, this procedure is not yet permitted in the United Kingdom. The HFEA originally precluded tissue typing for the benefit of a parent on the advice of its Ethics Committee.247 The Ethics Committee stated that, in this situation, a parent’s right to consent to donation on behalf of an incompetent child donor would be vitiated. However, the suggestion that the prospective child would not necessarily be loved or cared for any less was acknowledged. When reconsidering the issue three years later, the HFEA simply stated that the use of the PGD and HLA tissue typing to produce a donor for a parent ‘raises distinct and significant issues and recommended that this matter needed further consideration’.248

In support of allowing parents to undertake the procedure where it may help a loved one, whether or not it is a sibling, it has been argued that:

In liberal countries, the decision to have children is an area of private life in which the state may only intervene to prevent serious harms. Consequently in such countries if there is no reason to think the future child will be harmed, couples requesting PGD for HLA typing in order to have a donor child should be allowed to seek the necessary treatment.249

The Victorian Infertility Treatment Authority provides that PGD in conjunction with HLA tissue typing will only be available where the primary intended tissue recipient is a sibling; but should a relative have a similar genetic condition, a decision about further donation of cord blood or bone marrow resides with the parents of the child.250

The chances of achieving an exact tissue match between a child and a parent are extremely low. Further, it is unlikely such an umbilical cord blood transplant would offer greater chance of success than that which occurs with the transplantation of HSCs from an unrelated donor. Consequently, the scientific limitations present a considerable barrier to performing this procedure. However, the ethical concerns do not appear to be sufficient on their own to justify prohibition.

In the case of a partial match, cord blood could be used because of the greater tolerance of graft-versus-host disease; but subsequent donation of bone marrow or tissue would not be possible because of the haplotype mismatch. Significantly, no further demands could be placed on the donor child, which eliminates the potential for ‘exploitation’.

Providedthatthewelfareof thechildispromotedandprotectedbyprofessionalstandards and external oversight of parental decisions, there seems to be little justification for denying parents access to this technology if the procedure confers a clinically significant chance of recovery. It should be noted that there is no legal impediment to a parent being the recipient of cord blood from a naturally conceived child.

Section 4(a) of the Act requires that the ‘health, safety and dignity of present and future generations should be preserved and promoted’.251 The final criterion provided in the Guidelines requires a consideration of the health and well-being of the family. Taken together, the principle in the Act and the clause in the Guidelines place emphasis on the welfare of the family. This arguably augurs towards respecting

parental autonomy in decision-making, which in turn promotes the well-being of the parents and subsequently of the family as a whole.

It is well established that transplantation of HSCs from the umbilical cord blood of an HLA-matched sibling is currently the best course of treatment for children suffering from certain disorders affecting blood cell formation or the immune system. Permitting PGD with HLA tissue typing, when the established risks to a donor child are no greater than those associated with IVF and there is a reasonable chance of success, clearly promotes the health interests of the existing sick child and family and consequently the present generation.

Consideration of the health and well-being of the family requires an acknowledgement of the fact that the ordinary give and take of family life necessarily entails that, at times, the interests of one child may prevail over another. Parents must balance the sometimes-competing interests of their children, and their wider family. The interest involved for one child in the current context is the chance to live an ordinary life span. Conversely there are understandable but potentially speculative psychological risks to the donor child, which must be balanced. However, considerations regarding the health and well-being of families/whānau seem to mandate a more liberal approach to HLA tissue typing than is currently permitted by the Guidelines.

Section 4(g) of the Act provides that the different ethical, spiritual and cultural perspectives in society should be considered and treated with respect. Although ethical perspectives have been encompassed in the preceding analysis, when considering the current framework for HLA tissue typing it is also necessary to consider any additional arguments for restraint.

In an era where reference is increasingly made to the ‘rights’ of individuals, it has been suggested that it may eventually become accepted that a sick sibling has ‘a positive right against its parents that they take proportionate steps’ to provide a saviour sibling, and the resulting child has a positive obligation to assist the sick sibling.252 It is suggested that this web of ‘rights and responsibilities’, which initially appears to be an extreme proposal, might not be out of place in a future context if it became ‘commonplace’ for parents to engage in this technology.253

It is significant that the language of rights and obligations is associated with moral arguments both for prohibiting and permitting use of this technology. However, it is increasingly being used in support of permitting creation of saviour siblings. This is apparent in the following:

the argument that the parents have the right and to a certain extent the obligation to do what they can to save their child is a major reason for permitting the application.254

Another commentator has observed that the decision to have another child in order to save an existing child must be a matter of choice; although he ‘would not find it difficult to justify imposing a moral obligation in these circumstances’.255

Yet imposing such a moral obligation to undergo PGD with HLA tissue typing fails to take into account the physical, psychological and economic burden of performing PGD and HLA typing. The comparatively small chances of success and the fact that it necessarily involves introducing a new family member into a potentially stressed family situation are deterrents with regard to conception of a saviour sibling. Even if the creation of saviour siblings were to become more commonplace, it would constitute an extreme view that parents who were unwilling to engage in the procedure were neglectful, or abdicating their parental responsibility. In addition, the fact that parental pressure or coercion may eventuate in a future context is speculative, and does not justify the restriction of the procedure in the present.

It has been claimed that permitting HLA tissue typing will open the floodgates for the use of PGD for non-medical purposes.256 However, the slippery slope claim is flawed on at least two grounds. The first is that selecting for HLA type is not a frivolous choice but one which is directly associated with a serious, life-threatening disease process. It may be justified by the direct medical benefit accruing to another individual. As Mance LJ observed in the United Kingdom Court of Appeal, there is a distinction between performing embryo biopsy for trivial preferences, and performing it in the face of compelling medical situations. Tests for HLA compatibility lie conceptually between the two poles of ‘good medical reasons’ for tests and testing for ‘purely social reasons’, and they

lie closer in spirit in my view to the former pole than to the latter. There are here good medical reasons for screening any embryo, although they do not relate to any future child’s health. The concerns to which the authority’s decision ... are directed are anything but ‘purely social’, relating as they do to the health of a sibling and the well-being of the whole family.257

Secondly, it is difficult to see why HLA tissue typing might be permitted, whilst selection based on other non-medical characteristics which do not confer a health benefit is circumscribed. The permitting of HLA tissue typing where a sick sibling is in need of HSCT, as opposed to the permitting of PGD for non-medical purposes, offers a vivid moral demarcation. Additionally, any concerns regarding eugenics

do not gain traction in this context, as the purpose of the procedure is to cure a particular condition, not to eradicate a disease from the human gene pool.258 Slippery slope arguments verge on the irrational, and do not warrant limiting this technology given the purpose of the procedure.

A possible ethical concern in this context is the hypothetical use of an aborted foetus as a source of HSCs for transplantation. The same HSCs that are present in an umbilical cord at birth are present in the liver of a sixteen-week foetus, and could theoretically be used to provide a HSCT for a sick sibling.259 In the United States couples have enquired about conceiving an HLA-matched child and then undergoing an induced abortion to harvest the HSCs.260 Harvesting stem cells from an aborted foetus is illegal under federal law in the United States.261 At present there is no applicable law in New Zealand regarding the use of tissue or organs from an aborted foetus, and it is thus not directly prohibited.262

Although conception for termination and donation might generally run counter to moral intuitions, it may be a rational course of action for parents of a seriously ill child. It is potentially stressful to introduce a new baby into a family already coping with a seriously ill child. A family may wish to save their existing child, but not wish to extend their family at that particular time. Arguably, conception for termination may avoid problems if the transplant fails, as the child is not born into a grieving family, and will not feel guilt for the HSCT failure. Additionally, there is no child to ‘exploit’ for further tissue. One commentator has stated that this approach, which effectively avoids the birth of a child, may be ‘one way to remove all doubts about respect for future persons’. If HSCs can be harvested before viability, ‘problems of commodification and instrumentalisation of persons’ do not apply.263

There has been very little discussion about conception for donation after termination.264 It seems that clinicians and ethicists consider it to be, at the very least, ethically unacceptable, or even morally repugnant. This moral perturbation stems from the fact that terminations occur in the main because pregnancy is an unintended and unwanted occurrence of ordinary social life. In contrast, PGD and HLA tissue typing require considerable effort, resources and time. If this process were proposed, not for the purpose of implanting and developing a healthy foetus, but in order to terminate the foetus and harvest tissue, the nature and quality of the activity would change.

In the absence of foetal abnormality, an abortion during the first twenty weeks of gestation is rendered lawful if continuing the pregnancy would result in serious danger to the life, or the physical or mental health of the woman.265 In circumstances where a healthy foetus is intentionally conceived it is difficult then to claim that

termination is required for the mental well-being of the woman, particularly in the case of a late, second trimester abortion.

Performing HLA tissue typing on embryos necessarily requires the creation and destruction of embryos which are not a suitable match, or which are affected by a serious genetic disorder. Whilst destroying embryos is not a morally neutral act, it has been generally accepted as justifiable in the face of preventing or treating serious disease. However, a foetus is attributed a greater moral status which progressively increases the more developed it becomes, and it is a greater leap to justify a late termination.

New Zealand is not alone in addressing the saviour sibling issue. Consequently, it is worth considering the approach taken to the issue of saviour siblings in other jurisdictions.

PGD and HLA tissue typing became topical in Norway when the story of six-year-old Turkish boy, Mehmet Yildiz, was reported in the media.266 Mehmet suffers from the genetic disorder, beta thalassaemia major. The only curative treatment for the disease is HSCT from a related HLA-compatible donor which has a success rate reported to be above 90 per cent.

According to legislation which came into force in January 2004, PGD is restricted in Norway to serious, X-linked diseases where there are no other possibilities for treatment.267 As thalassaemia is an autosomal recessive condition, it did not come within the indications for PGD; nor was HLA tissue typing permitted under the Act. Mehmet’s case was televised a month after the Act came into force. The underlying message of the broadcast was that, without HSCT, Mehmet’s condition was terminal. After the programme screened, the Progressive Party called for a law change that would permit children with serious diseases in need of HSCT to have access to treatment, regardless of the origin of the disorder. The Progressive Party subsequently proposed a Bill which would have amended the Biotechnology Act of 5 December 2003, but which was strongly opposed by the Minister of Health.

The Socialist Leftist Party, which had supported the Government coalition in the parliamentary debates on the legislation, came under heavy pressure to change its stance on PGD. It subsequently proposed an exemption to the ban on PGD if and when ‘particular considerations speak in favour of a case’. The reference to ‘particular considerations’ meant the ‘presence, or the risk, of serious genetic disease without treatment possibilities’. An independent medical Ethics Committee was empowered

to grant the exemption and to evaluate individual applications for the performance of PGD to conceive a child unaffected by a serious genetic disorder, as well as to evaluate the use of HLA typing to conceive a compatible donor for a sibling suffering from a genetic disorder. A Bill was passed to incorporate these amendments in May of 2004. (It would have been interesting to see if the outcome had been the same if Mehmet’s illness were not genetic in origin.)

It was claimed that the Socialist Leftist Party changed its position for several reasons. These included not only the pressure exerted by the media campaign but also the fact that the restrictive policy was not able to be defended in the face of its ‘first reality test’ and the better arguments made in the ensuing debate.268 It is important that the New Zealand policy regarding HLA tissue typing is sufficiently robust to withstand its first ‘reality test’.269

The Health Council of the Netherlands (an independent scientific advisory body whose task it is to advise Ministers and Parliament in the field of public health) recently advised that the life-threatening nature of a disease can justify HLA tissue typing in cases where parents are able to love and nurture the child. The Council also observed that whether or not the condition of the affected child is hereditary is not of critical importance. Selection has an indirect medical motive: the curing of the sibling.270 The Secretary of State, however, did not endorse this advice, and PGD carried out in the absence of a genetic risk to the embryo remains prohibited in the Netherlands.271

In Denmark, PGD is permitted if there is a risk of transmission of a serious genetic disorder.272 In 2004, an amendment was passed which permits PGD and selection on the basis of HLA tissue type.273 Under this provision the Minister of Health may authorise PGD with HLA tissue typing where a compatible donor is required for a sibling suffering from a serious disease.274 It is not a requirement that the disease suffered by the affected child is hereditary.

In Sweden PGD is regulated by guidelines promulgated by the Government and Parliament and is restricted to diagnosing severe, progressively developing hereditary disorders which could lead to early death and for which there is no available treatment.275 The Committee on Genetic Integrity has not yet come to a decision regarding tissue typing.

The Victorian Infertility Treatment Authority (ITA) restricts the performance of HLA tissue typing to circumstances in which the existing child has a severe or life- threatening genetic disease.276 However the Victorian Infertility Treatment Act 1995 only permits access to assisted reproductive services in the case of infertility, or where there is a risk of transmission of a genetic disorder. This restricts the discretion of the ITA to permit HLA tissue typing in the absence of a genetic risk to the prospective child.277 The New Zealand policy body is not restricted in the same way. The ITA Guidance provides that the resulting child, born as a result of the procedure, should only provide cord blood or bone marrow, and stipulates that the harvesting of ‘hard’ or non-regenerative organs is not acceptable.278

HLA tissue typing is approved by the HFEA on a case-by-case basis. Applications are expected to demonstrate that all possible alternative treatments have been investigated, and to show why preimplantation tissue typing is the preferred option. It is expected that tissue typing will only be undertaken for an existing child with a serious or life-threatening condition, and this condition is not limited to diseases that are genetic in origin.

The ESHRE Ethics Task Force has stated that HLA tissue typing is morally justified if the potential child’s use as a donor is not the only motive for the parents to have the child.279 Performing PGD for the creation of an HLA-matched sibling to cure a sick child with a serious non-genetic disease is also deemed acceptable. However, it has stated that, given the low chance of success, it may be inappropriate to recommend the course of treatment ‘in cases of advanced maternal age and/or poor ovarian reserve’.280 ESHRE has also recommended that follow-up should be performed as reliable empirical research is required to determine the psychological and social consequences for the donor sibling. For this reason, a register should be set up to record donations.

The majority of the jurisdictions covered in this brief overview permit the use of HLA tissue typing with PGD to conceive an HLA-matched child. Whether the disease suffered by the sick sibling is genetic in origin is immaterial in both the United Kingdom and Denmark. Proposals to extend HLA tissue typing where there is no genetic risk have occurred in two jurisdictions, but have been unsuccessful. Both the United Kingdom and Victorian jurisdictions countenance the transplantation of bone marrow tissue from a child conceived by PGD and HLA tissue typing.

The best justification for State intervention in this context is the concern that children may be exploited as donors in violation of their dignity. Yet it is also possible that the creation of saviour siblings may be perceived from within a human rights framework.281 Within such a rights framework, individuals have ‘positive obligations to assist one another’ in some circumstances when they can do so at little or negligible cost to themselves.282 There seems to be support for this sentiment in surveys undertaken to assess the views of the public.

In a large survey of Americans, undertaken by the Genetics and Public Policy Centre, John Hopkins University, the majority of respondents approved the use of PGD to select an embryo that was a match for a sick sibling. Strong support was reported for such a technology when it provides a health benefit, even when that benefit accrues to another person.283

When reviewing its Guidance on Preimplantation Tissue Typing, the HFEA commissioned research into public opinion on issues related to embryo selection for tissue typing and sibling cord blood and bone marrow donation.284 A series of workshops consisting of six groups comprising six to eight members of the public was conducted. Two of these groups had ‘direct interest in either genetic disease or assisted conception’. To investigate how public opinion on these issues was formed and influenced, these groups met to discuss the issues and to develop their opinions on the use of assisted reproductive technologies. The same individuals were then brought together, for a half-day workshop with experts, to explore their views further.

It was reported after the initial discussion that participants’ views were ‘broadly in favour of the use of any technique which could save the life of a child, as long as the risks were well managed’. The majority of participants did not consider it important whether the condition suffered by the sick sibling was hereditary. What was important was the seriousness of the condition affecting the sick sibling. However, many of the participants expressed greater reservations about the use of the procedure to produce a bone marrow donor. Reportedly, these views changed after discussion with an expert.

Parents have been attempting to conceive potential donors for seriously ill siblings ever since it was possible to diagnose certain medical conditions and HLA tissue type prenatally. The fact that this can be achieved more easily and with greater accuracy with the use of PGD does not mean that it should necessarily be integrated into mainstream medicine without careful analysis. Whilst the HART Act 2004 seeks to secure the benefits of assisted reproductive technology, it is also concerned to protect the health, safety, dignity and rights of all individuals in the use of such technologies.

The ability to create saviour siblings utilising PGD technology has called into question what constitutes responsible parenthood and the legitimate scope of parental decision-making authority. It has resulted in the formulation of guidelines, which now have legal status under the HART Act 2004.285 This section has analysed the risks and benefits of HLA tissue typing, as well as the arguments in favour of and against liberalising the current guidelines. It concludes that the current restrictive HLA policy is both ethically and legally problematic.

Significant benefits accrue from HLA tissue typing in conjunction with PGD. It is widely accepted that transplantation of umbilical cord blood HSCs from an HLA- matched sibling provides the best chance, or possibly the only chance, of successful treatment for children suffering from certain disorders. The physical risks to a donor child conceived for this purpose are not high. They comprise the ordinary risks associated with IVF and embryo biopsy as well as a relatively small additional risk in the case of low birth weight or preterm babies. The psychological sequelae for children conceived to be cord blood donors are not yet established. They will only be deduced after sufficient time has elapsed for qualitative research to be undertaken. In the interim, the issue is whether the concerns outweigh the potential or, in some cases, inevitable death of a child.

The HART Act 2004 requires that the health and well-being of a child born as the result of an assisted reproductive procedure is an important consideration in all decisions about that procedure; but it is not a paramount consideration, nor is it the only consideration. Equally, the Act requires that the human health, safety and dignity of present and future generations should be preserved and promoted. Permitting parents to conceive an HLA-compatible sibling provides a seriously ill child with a chance of disease-free survival. This clearly promotes the health of the existing child and the well-being of the family and, potentially, the next generation. These principles and the first purpose of the Act support reproductive liberty and provide strong support for a less restrictive policy.

The Act also requires that the different ethical perspectives in society should be considered and treated with respect. Concerns regarding responsible parenthood and instrumentalisation of the donor child are insufficient to displace the interests of parents who wish to undertake this clinical course when there is a reasonable chance of success, and the interests of the sick child who will have an opportunity for survival. Conception of a child to be a donor is no worse or less altruistic than the multitude of other reasons for conception of a child. Indeed, the decision to conceive a child who may provide HSCs for a sick sibling perhaps constitutes one of the more rational reasons for conceiving a child.

Concerns that a donor child may face ongoing requests for donation are valid, but may be managed by standards of clinical practice. They are not sufficient on their own to justify restricting the performance of HLA tissue typing. Slippery slope arguments are weak and fail to provide sufficient justification for limiting HLA tissue typing given the purpose of the procedure. Whilst there may be ethical concerns for the welfare of donor children, which mandate caution, what can be said is that:

it is far from obvious that considerations of child welfare should count against, rather than for, the practice of saviour sibling selection.286

It has been argued on a clause-by-clause basis that the Guidelines are problematic, and require revision. There is no good reason to restrict HLA tissue typing to circumstances where the sick child is suffering from a single gene or sex-linked disorder, as there is no valid moral distinction between performing PGD and HLA tissue typing in the presence or absence of a genetic risk. The Guidelines should simply require that the sick sibling is suffering from, or has suffered from, a condition which is serious or life threatening.

The restriction, which limits performance of PGD with HLA tissue typing to situations where there are no other possibilities for treatment or sources of tissue available, is unduly onerous. Cord blood registries may contain a reasonable match for the sick child in some cases, but a sibling HLA match may constitute the best chance of a successful outcome. In addition, parents may wish to conceive a donor child in the event that the therapy currently being undertaken by the sick child is unsuccessful. It would be preferable to require that ‘all other possibilities of treatment and sources of tissue for the affected child have been explored’.

Finally, whilst the purpose of conceiving an HLA-matched child is relevant to decision-making under the Act, it is not within the jurisdiction of ACART to impose limits on tissue donation after a child is born. Sibling bone marrow donation has occurred with naturally conceived children who are an HLA match with a sick sibling in accordance with the general law regarding incompetent minors. It is argued here that there is no relevant moral objection to permitting bone marrow donation if a cord blood HSC transplant fails, or is unable to be performed. This should be a matter for parental and clinical decision-making, taking into account the clinical circumstances of the infant or child and the sick sibling, and based on the usual legal standard for the provision of proxy consent. There does not appear to be any evidence that deference to parental autonomy in relation to providing proxy consent to bone marrow transplantation has led to an inappropriate exercise of parental authority in the past. However, good medical practice should dictate that the donor child has an independent physician and an appropriately qualified independent advocate who may act on the child’s behalf. Whenever there is doubt regarding the appropriateness of the procedure, the jurisdiction of the Family Court should be invoked.

It is manifestly reasonable to state that good medical practice would dictate a limit to the number and type of procedures which may be performed on an incompetent saviour sibling for the benefit of a sick child.287 However, imposing a precise limit may be an arbitrary restriction. It may be of greater value to appoint a professional advocate for a child, such as a child psychologist, who is able to communicate with the child and is independent of the parents and the physicians. Such an appointment may best achieve the protection and promotion of the donor child’s interests. In the case of disagreement, any eligible persons involved should apply to the Court for determination.

Introducing a register to record all those children born as a result of preimplantation HLA tissue typing, and to record subsequent tissue donations, is imperative so that empirical studies may be undertaken on the effects on donor children which may inform subsequent policy-making.

Conception of a child who may provide cord blood or bone marrow for a sick sibling should be permitted where as well as wanting a donor child the child is wanted in its own right and:

A register should be set up by the Ministry of Health to record the birth of all children born from PGD with HLA tissue typing, and to record subsequent tissue donation. Parents must agree to participate in follow-up studies if and when they are undertaken.

Source: K. Moise, ‘Umbilical Cord Stem Cells’ (2005) 106 Obstetrics & Gynecology 1393, 1394

* Personal communications: Mark Walters, MD, of Children’s Hospital Oakland Research Institute and Joanne Kurtzberg, MD, Director Carolinas Cord Blood Bank at Duke

The use of PGD to diagnose and select against embryos which are affected by serious single gene or chromosomal disorders is permitted as a routine clinical procedure by virtue of the HART Order 2005. However, as was observed in the first report of the Human Genome Research Project, the position regarding negative selection of unaffected carrier embryos is equivocal.288 Embryos which are ‘unaffected’ or ‘healthy’ carriers of a genetic mutation have an allele which is associated with a particular genetic disorder, but have also inherited a normal allele which is dominant. These heterozygote carrier embryos, if implanted and carried successfully to term, will not be born with any clinical manifestations of the relevant genetic disorder, but will be an unaffected ‘carrier’ of the familial mutation. Individuals who are healthy carriers of a heritable mutation do not, with some exceptions, have any phenotypic characteristics of the genetic disorder, but are capable of passing on the genetic condition to their future offspring.

The current regulatory scheme restricts the performance of PGD on a strictly therapeutic normative basis. PGD may only be performed to prevent the transmission of disorders capable of causing serious impairment in a future individual. As yet, the established procedures policy does not expressly provide for the negative selection of carrier embryos.

Two developments in particular signal that the issue of preimplantation selection of embryos and the status of unaffected carrier embryos will become a significant topic in the context of PGD. First, as science provides more choices for genetic selection, it also provides better treatment and improved quality of life for people with inherited genetic conditions such as haemophilia or cystic fibrosis.289 More people affected by serious genetic disorders may now live to reproductive age and beyond. They may consider parenthood, and reprogenetic technology, when they might not have done so if they had been born even a decade before. Secondly, as PGD technology becomes more sophisticated and accurate and is performed more regularly, more embryos will be identified as carriers of recessive disorders and prospective parents may want a choice as to which are implanted.

This section explores whether the arguments that have been raised against PGD simpliciter are enhanced in the case of PGD, which may result in selection against healthy carrier embryos. It clarifies at the outset the different implications of being a carrier of an X-linked recessive disorder as opposed to being an unaffected carrier of an autosomal recessive disorder. The effect of the current New Zealand law in relation to the negative selection of carrier embryos is considered, and an overview

is provided of other jurisdictions that have considered this issue. Ultimately, this section considers who should decide whether carrier embryos may be negatively selected, and according to what criteria.

When selecting against carrier embryos, the genetic condition for which a prospective carrier is at risk impacts greatly on the implications of carrier status. Although a female carrier of an X-linked recessive disorder such as Duchenne muscular dystrophy is unaffected, the risk of passing the disorder on to a future son is 50 per cent.

In contrast, for a carrier of an autosomal recessive gene (whose reproductive partner is not a carrier) the risk of passing on the disorder may only be 1 per cent,290 or even less.291 Clearly, the reproductive risk for a carrier of an autosomal recessive condition is much lower. Consequently, there is a significant distinction between healthy carriers of X-linked recessive conditions and heterozygote carriers of autosomal recessive conditions. This factor necessarily affects the nature and quality of negative selection in these circumstances.

Although the issue of carrier status is often referred to in terms of the ‘reproductive risk’ for the carrier, it is not merely reproductive interests that are of concern in the case of some recessive conditions. It is possible that carriers of certain recessive disorders may manifest phenotypic symptoms. An example of this is X-linked adrenoleukodystrophy. Although this disorder is inherited in an X-linked pattern, carrier females can exhibit symptoms of the condition.292 Such a clinical scenario arguably fits within a therapeutic PGD framework, rendering negative selection in these circumstances permissible; or at least enhancing the arguments in favour of selecting against carrier embryos in this context.

Construing the interests at stake simply as ‘reproductive interests’, as opposed to health interests, may not be a true reflection of the implications of carrier status on future individuals, particularly in the case of carriers of X-linked conditions. In addition to potentially imposing a physical burden on the prospective carrier, an individual’s carrier status may also impose a significant psychological burden. This burden rewrites the rules of engagement not only for pregnancy, but also potentially the relationships that carrier offspring may develop.

There are two possible situations when the issue of selecting against carrier embryos using PGD may arise. The first and most likely situation is when PGD is indicated because of the risk of passing on a serious hereditary disorder, and selecting against carrier embryos becomes a contingent or additional possibility. For the purposes of this discussion it will be described as ‘contingent selection’ (i.e. secondary or additional selection).

The second possible situation occurs when an individual who is not at risk of having an affected child wishes to avoid having a child who will be an unaffected carrier child; this will be referred to as ‘primary purpose PGD’. Requests to perform PGD to negatively select an unaffected carrier are more likely to occur in the case of X-linked recessive conditions where an affected male wishes to avoid passing the mutation on to a daughter, who would be at risk of transmitting the disorder to her sons. The distinction between selecting against carrier embryos on a contingent basis versus a primary basis is made in the following example using the case of haemophilia.

A female carrier of haemophilia has a 25 per cent chance of conceiving a son affected by haemophilia, and a 25 per cent chance of having a healthy daughter who is a carrier of the haemophilia mutation. In this example the possibility of selecting against a carrier daughter is a secondary possibility as a result of PGD, which is principally performed to avoid the transmission of haemophilia to a son. The possible reproductive outcomes for a female carrier of the X-linked disorder haemophilia are represented in Table 1:

Pregnancy outcome	Probability	clinical problems	implications for next generation
A Male with haemophilia	25 per cent	Bleeding tendency, lifelong therapy	Daughters 50 per cent risk of being carriers
B Healthy Male	25 per cent	Nil	Nil
C Carrier Female	25 per cent	90 per cent healthy, 10 per cent mild bleeding	Daughters 50 per cent risk of being carriers, sons 50 per cent risk for haemophilia
D Healthy Female	25 per cent	Nil	Nil

Table 1: Reproductive outcome for a female carrier of X-linked haemophilia

The other category entails the utilisation of PGD to avoid the creation of healthy carrier offspring as a primary goal. PGD is engaged in solely to deselect a carrier embryo. This could occur in the case of a haemophiliac male. He cannot pass the mutation on to any prospective sons because it is an X-linked condition. However, any prospective daughters will be carriers. In these circumstances PGD is performed where there is no risk of transmitting the genetic disorder, but there is a risk of transmitting carrier status to female offspring. The possible reproductive outcomes in this situation are represented in Table 2:

Pregnancy outcome	Probability	clinical problems	implications for next generation
A Healthy male	50 per cent	Nil	Nil
B Carrier female	50 per cent	90 per cent healthy, 10 per cent mild bleeding	Daughters 50 per cent risk of being carriers, sons 50 per cent risk of haemophilia

There are no reports, as yet, of a demand for PGD where no risk exists of having a child affected by a serious genetic disorder, but where there is a risk of transmitting carrier status to offspring, i.e. primary purpose PGD. However, the same is not true in the case of prenatal diagnosis and X-linked genetic disorders. Requests have been made for prenatal diagnosis of carrier status in relation to haemophilia A and fragile X syndrome, both X-linked recessive disorders.293 The parents requesting prenatal diagnosis were prepared to terminate not only an affected male foetus, but also a female foetus if it were diagnosed as a carrier of the particular X-linked recessive disorder.

As has already been observed, female carriers of X-linked disorders do not generally manifest any phenotypic symptoms; only males who inherit the abnormal gene are affected. However there are exceptions to this. In some cases females will exhibit effects of the X-linked recessive mutation that they are carrying. Approximately 10 per cent of female carriers of the haemophilia A gene, for example, may display a mild bleeding tendency. In the case of fragile X, the most common inherited form of mental retardation apart from Down syndrome, carrying a premutation has no observable phenotypic impact on female offspring; but female carriers of full mutations can be affected.294 Whilst there may be evidence that a female carrier foetus of fragile X syndrome will be affected, there is only a small risk that a female carrier of haemophilia will be mildly affected.

It was reported that the motivation of the parents who presented for prenatal diagnosis of carrier status was to expunge the haemophilia and fragile X disorders from their families.295 Clearly, there is evidence that some prospective parents have a strong desire to avoid the transmission of carrier status to their offspring. If being a carrier of an X-linked recessive disorder poses a reasonable risk of phenotypic manifestations, negative selection of ‘healthy’ carrier embryos may be justified on health grounds. However, when carrier status may only pose a risk of a ‘minor’ genetic abnormality or no abnormality at all, selection against broadly ‘unaffected’ carrier embryos can represent a considerable moral dilemma.

There is evidence that some parents would consider termination if a foetus were a female carrier of a serious X-linked disorder. With the introduction of PGD, avoiding carrier offspring is now possible at the preimplantation stage. When PGD has been performed to diagnose serious heritable disorders, and carrier status has been determined in the process, it is a matter of debate whether selection on the basis of unaffected carrier status should be permitted, and who should decide. A more problematic issue is whether PGD should be accessible to parents who are not at risk of having offspring affected by a particular serious genetic disorder, but who may transmit the recessive allele to the following generation. This analysis considers whether negative selection of carrier embryos is permitted under the current legal framework and, if not, whether it should be. It concludes that the law is unclear, but that there is no principled basis to prevent parents from choosing to avoid implantation of carrier embryos.

In the course of ordinary IVF the embryologist is responsible for selecting the best- quality embryo or embryos for implantation. This involves selecting the embryo with those characteristics conferring the greatest chance of implantation and of being successfully carried to term. However, performing PGD for single gene disorders brings an additional dimension to embryo selection. This is because some embryos will be affected by a single gene disorder, some will be unaffected and some will be unaffected carriers of the relevant mutation. Although carrier status is not always diagnosed in the course of preimplantation diagnosis, some tests will indicate unaffected carriers as an unavoidable by-product of preimplantation testing.

There are two related issues. The first is whether parents have a right to know the carrier status of their embryos and second is whether they should be permitted to select against carrier embryos.

The following passage seeks to determine what information parents are entitled to receive in the course of PGD. The related issue, whether parents ought to be able to select against carrier embryos, will then be considered.

The Code of Health and Disability Services Consumers’ Rights establishes the civil standard for the provision of health services by health care providers to health care consumers in New Zealand.296 The Code, promulgated pursuant to the HDC Act 1994, declares that consumers have rights and providers have duties.297 The Code encompasses both providers and consumers of fertility services, and imposes extensive information requirements on providers. To determine the relevance of the Code to the performance of PGD, it is necessary to unpack not only the rights, but also the relevant definitions provided in both the Code and the HDC Act 1994.

Right 6(1) of the Code provides that ‘every consumer has the right to the information that a reasonable consumer, in that consumer’s circumstances, would expect to receive’, including the results of tests (6(f)) and the results of procedures (6(g)). (Emphasis added.) Clause 4 of the Code provides that a ‘consumer’ is a health consumer. The definition of a ‘health consumer’ is provided in section 2 of the HDC Act 1994, which declares that a health consumer ‘includes any person on or in respect of whom any health care procedure is carried out’. A ‘health care procedure’ is further defined as any health treatment, health examination, health teaching or health research administered to or carried out on or in respect of any person by any health care provider; and includes any provision of health services to any person by any health care provider. The definition of ‘health services’ in section 2 of the Act includes diagnostic services and fertility services.

Embryo biopsy is clearly a diagnostic procedure, which comes within the meaning of a ‘health service’. The question is whether embryo biopsy comes within the definition of a ‘health care procedure’. Diagnosing embryos for genetic abnormalities constitutes a health examination. The issue is whether it is carried out ‘on or in respect of any person by any health care provider’. The embryologist comes within the definition of a ‘health care provider’ contained in section 3 of the Act. However, as the embryo is not a person, the procedure is not carried out ‘on any person’.298 To come within the definition of a health care procedure, the biopsy must be carried out ‘in respect of any person’. The biopsy is not carried out on a body part or tissue provided by the mother, but on a separate entity created by in vitro fertilisation. In this context, it is possible that the embryo biopsy, whilst it is a health service, is not a health care procedure carried out on or in respect of any person. Therefore, the right to be fully informed of the results of the testing is potentially not triggered under the Code.

However, it would be difficult to sustain this line of argument when an embryo is selected for transfer. The process of implantation clearly comes within the definition of a health care procedure carried out on a health care consumer, with the corresponding right under 6(1) of the Code to be fully informed with regards to the implantation procedure. On this analysis, the right to be fully informed under the Code arises in the context of implantation, but does not necessarily arise as a matter of course when the results of embryo biopsy are known. Whether it should arise at the point of diagnosis is a moot point.299

If selection against unaffected carrier embryos is permissible under the established procedures order, there may be no reason to refuse disclosure of the information. However, if selection against carrier embryos is not permitted under the HART Order 2005, it could create significant difficulties for a provider if parents wished to know in advance and consequently attempted to influence embryo selection.300 If negative selection of unaffected carriers is not permitted, then it is arguable that a reasonable consumer in that consumer’s circumstances would not expect to be privy to that information at the point of biopsy; but it could be reasonable to expect to be informed of carrier status of any embryos selected for implantation. Information regarding carrier status of an embryo is health information and is information that a reasonable consumer, in that consumer’s circumstances, may expect to receive in the course of embryo transfer.

The caution exercised by clinicians worldwide in relation to the performance of carrier testing on minors, and the disclosure of carrier information, may be relevant to the disclosure to parents of carrier status determined as a result of PGD. A recent systematic review, which examined fourteen guidelines from various jurisdictions, revealed that all of the guidelines were unanimous in recommending that carrier testing in minors should not be performed, but should be deferred until the child could give informed consent to testing.301 It was stated that:

Despite the lack of conclusive evidence that carrier testing performed during childhood harms children psychologically,302 the great majority of genetic testing guidelines espouse the premise that carrier testing might be detrimental to the mental well being of tested children, and as such, should be disallowed in children.303

However two bodies, the British Medical Association and the United Kingdom Genetic Interest Group, have a more flexible stance regarding the testing of minors. In their view, providing information to a minor regarding carrier status could help a child to cope with this knowledge from an early age and could ‘reduce the anxiety and uncertainty experienced by parents about their child’s carrier status’.304

When carrier status is discovered incidentally (which may occur in the course of PGD or in newborn screening) the British Medical Association guidelines and the American Academy of Pediatrics recommend that carrier status results should be conveyed to parents. However, the American Medical Association and the German Society of Human Genetics recommend that the child’s carrier status should not be disclosed to parents or to other third parties.305 They suggest that the information regarding carrier status should be ‘discussed with the child when he reaches reproductive age’. The American Medical Association guidelines also provide instructions for maintaining confidentiality, and state that this ‘privileged information’ should be kept separately from a patient’s medical record to avoid inadvertent disclosure. Yet it seems that there is a paucity of evidence regarding the beneficial or detrimental effects of carrier testing and disclosure to minors.

As discussed, it is likely that parents may wish to know the carrier status of embryos created and implanted in the course of PGD. It seems counter-intuitive to withhold information regarding carrier status given the seriousness of the genetic disorders involved, and the lack of evidence regarding harm in disclosure of such information. However, there is evidence that some organisations recommend not disclosing carrier status when it is discovered incidentally. Two organisations, the British Medical Association and the American Academy of Pediatrics, provide that disclosure of carrier status to parents is acceptable. Given the lack of evidence regarding harm, the balance seems to be in favour of informing parents of the carrier status of embryos created and embryos transferred for implantation.306

Right 7(1) of the Code provides that ‘services may be provided to a consumer only if that consumer makes an informed choice and gives informed consent, except where any enactment, or the common law, or any other provision of this Code provides otherwise’. Right 7 does not confer on consumers a choice regarding the implantation of a non-carrier or carrier embryo if it has been legally precluded by the HART Order 2005. Right 7 simply maintains a consumers’ right to informed consent as is generally required in the health context. It is consequently necessary to determine whether negative selection against carrier embryos is permitted under the Order.

The current legal position under the HART Order 2005 is as follows. PGD may be performed as an established procedure for familial single gene disorders where the disorder has been identified in the family, there is a 25 per cent or greater risk of an affected pregnancy and the future individual may be seriously impaired as a result of

the disorder. Sex selection is also permitted in the case of familial X-linked disorders where there is no specific test for the particular disease-causing mutation available, there is a 25 per cent or greater risk of an affected pregnancy and the future individual may be seriously impaired as a result of the disorder. PGD which falls within these categories may be carried out as a routine clinical procedure.

A rigid interpretation of the established procedures order may suggest that intentional selection against healthy carriers in the course of PGD is not permitted because positive carrier status is not a serious impairment. However, it could be argued that transmission of carrier status is capable of causing serious impairment in a future individual in some instances.

Being a carrier of an X-linked or autosomal recessive disorder undeniably associates an unaffected carrier embryo with a particular genetic disorder. However, carriers of X-linked conditions are burdened more directly. Female carriers of X-linked recessive mutations have a one in two risk that prospective sons will inherit and develop the disorder, and a one in two chance that female offspring will also be carriers. In the case of carrier daughters, there is a 25 per cent chance that a future grandson will be affected. Because of the statistical risk of transmission, selection against unaffected (female) carriers of X-linked disorders meets the criteria provided in the Order, and may arguably be carried out as an established procedure.

However, carriers of autosomal recessive disorders will only be burdened by the mutation if they reproduce with a partner carrying the same recessive disorder, so the risk of an affected pregnancy is much lower. It is unlikely that being a carrier of an autosomal recessive disorder would generally be characterised as a serious impairment, unless it were open to a subjective assessment. Serious impairment is not defined in the HART Order 2005.

Regardless of whether the transmission of healthy carrier status is categorised as causing serious impairment, it is possible that selection against carrier embryos may be a legitimate activity in the course of PGD performed to prevent the direct transmission of the disorder. It is reasonable to interpret the Order as merely providing threshold criteria for accessing PGD, with subsequent selection decisions being left to the clinicians and parents involved.

There is a precedent for this type of approach in other similar jurisdictions. In the United Kingdom the HFEA’s Code of Practice declares that PGD should only be considered where there is a ‘significant risk of a serious genetic condition being present in the embryo’.307 However, it is clear that some clinics in the United Kingdom have a policy of preferentially transferring unaffected embryos first; and, if there

aren’t any, they will then discuss with parents the possibility of implanting carrier embryos.308 The HFEA has acknowledged that selection against carrier embryos may occur as a result of the PGD process, although it seems there are no formal guidelines for practice.

The effect of the current regulatory framework is that if selection against carriers is not permitted under the established procedures category, and it is not an expressly prohibited activity under the Act, then it is by default a regulated activity. The only application of PGD which is expressly prohibited by the HART Act and the Guidelines is PGD performed for social reasons.309 As selection against carrier embryos is based on a disease-related genotype, it would be inaccurate to consider it to be social selection. It is therefore not prohibited, and falls into the regulated category if it is not covered by the established procedure Order. A regulated activity may not be carried out unless it is carried out in accordance with Guidelines promulgated by ACART.310 In the absence of Guidelines, the procedure may not be lawfully performed.

There is a major distinction between performing PGD to negatively select carrier embryos as a primary goal and performing it as a contingent or additional procedure to avoid conception of a child who will manifest symptoms of the disease. In the latter case the PGD cycle and embryo biopsy is, arguably, a medical imperative because the future individual may be directly affected. Embryo biopsy is justified in the case of contingent PGD because of the risk of disease transmission; testing for carrier status is merely a contingent activity. However with primary purpose carrier selection, the only reason for performing PGD is to determine the carrier status of otherwise healthy embryos.

The legality of performing PGD with the primary purpose of negatively selecting embryos which are healthy carriers of recessive disorders differs according to whether the disorder is X-linked or autosomal recessive. PGD carried out for the primary purpose of preventing the transmission of carrier status in the case of X-linked disorders arguably comes within the established procedures order. In the case of a male with haemophilia, his offspring will not be affected, but his daughters will all be carriers. Hence, the risk that a future grandson will have the disorder is 25 per cent.311

This situation meets the criteria in the HART Order 2005, as there is a 25 per cent or greater risk of an affected pregnancy and evidence that the future individual may be seriously impaired as a result of the disorder. Consequently PGD may arguably be performed in the case of X-linked disorders, when the primary purpose is selecting against a healthy carrier embryo, as an established procedure.

The risk of transmission for autosomal recessive disorders arguably does not meet the threshold. Although there is a 50 per cent chance that an individual who is a carrier of an autosomal recessive condition will pass on carrier status to offspring, the reproductive risk to the future offspring (i.e. the grandchildren) may be less than 1 per cent. Consequently, the legality of performing PGD as an established procedure to detect carrier status of an autosomal disorder as a primary purpose depends upon whether carrier status alone is construed as causing serious impairment.

Ultimately the current legal position regarding selection against healthy carrier embryos in the course of PGD is unclear. A literal interpretation of the established procedures Order would suggest that selection against healthy carriers is not permissible in the case of autosomal recessive conditions, but is possibly permissible for X-linked conditions. However, it is arguable that selection against carrier embryos of both autosomal and X-linked conditions may occur at the very least as a contingent procedure to ordinary PGD covered by the established procedures Order. According to this view, once the threshold for PGD is met selection against carrier embryos may be permitted in the case of contingent PGD as an exercise of clinical and parental decision-making.

It is also plausible that selection against X-linked carriers may be legally performed as a primary procedure under the established procedures category. Selection against healthy carriers of autosomal recessive disorders as a primary procedure is not arguable on a literal interpretation of the established procedures Order, because of the required 25 per cent or greater risk of an affected pregnancy; unless being a carrier of an autosomal recessive disorder constitutes serious impairment in itself. This is almost impossible to argue, because the entire population would be seriously impaired.

Ultimately there are two distinct questions: first, whether selection against carrier embryos is permitted under the current law; and, secondly, if it is not permitted, whether it should be. As explained earlier, the answer to the former is not clear- cut. The following is concerned with the second question and considers whether the purpose and principles of the HART Act 2004 support permitting carrier testing either as a contingent procedure to ordinary PGD or as a primary purpose.

This section examines whether selection against carrier embryos should be permitted either as a contingent or primary procedure. The framework proposed in the second section of this report will be used to consider this question. It starts from a presumption of reproductive autonomy and then takes into account the relevant principles of the Act. The relevant principles include the provision that the health and well-being of children born should be an important consideration in all decisions regarding a procedure; the health, safety and dignity of present and future generations should be preserved and promoted; and the different ethical, spiritual and cultural perspectives in society should be considered and treated with respect. The arguments in favour of negative selection of carrier embryos are considered first, followed by the arguments against carrier testing. While the arguments against carrier testing must be accorded respect, it is argued that they should not displace the arguments in favour of reproductive liberty and parental choice.

Arguments in favour of permitting selection against carrier embryos may be made on the grounds of reproductive liberty or the reproductive interests of the future child. They may also be predicated on the grounds of intergenerational benefit. Conversely, moral barriers to permitting selection against carrier embryos may be made on the grounds that it involves the destruction of healthy embryos, that it is an exercise based on genetic essentialism, that it harms society by reducing genetic diversity or that it stigmatises healthy carriers.

The standard justification for permitting selection against embryos carrying recessive disorders is to prevent carrier offspring from facing the same reproductive issues as their parents. The relevant issue is whether there are sufficient reasons or harms to restrict prospective parents from selecting against unaffected carrier embryos, either contingently to PGD, when it is performed to diagnose a serious disorder, or as a stand-alone primary purpose procedure.

As already discussed, the justification for selecting against unaffected carriers is generally based on the reproductive implications for the carriers, not the prospective health of the grandchildren or the intergenerational effects. For the vast majority of carriers of autosomal recessive conditions, who reproduce with non-carriers, carrier status will not be an issue. In addition, carriers will have the same reproductive options available to them as currently exist, such as prenatal genetic diagnosis or PGD. Hence the means to prevent the transmission of deleterious mutations will be available.

Yet it is easy to over-simplify the implications of carrier status as simply impacting upon reproductive freedom. Not all carrier offspring will engage in reprogenetic

technology. They may conceive, carry and deliver affected offspring, whether intentionally or not. Not all pregnancies are planned, nor do all those at risk of having affected children wish to engage in preventive technology. It is undeniable that raising a child with a severe X-linked recessive disorder causes a parent or parents significant mental anguish. Hence, selecting against carrier embryos may not be viewed simply from the perspective that harm is avoided for the next generation; potential harm to subsequent generations is also prevented. A wish to avoid carrier offspring may stem from the parents’ desire to prevent a putative child experiencing the guilt of passing on a deleterious gene, and consequently suffering significant psychological or emotional distress through witnessing the suffering of a child affected by a disorder for which they feel responsible. This mental anguish has been vividly described by a carrier mother of a son affected by haemophilia in the following statement:

How often do we hear or make the statement, ‘Hemophilia affects males and is passed on by females.’ Here lies the seed that grows into that canker called guilt which lies heavily on the hearts of many carrier mothers.312

As argued above, the potential reasons for selecting against carrier embryos may extend beyond the reproductive interests of future offspring to intergenerational considerations. Nevertheless, it should not be assumed that exclusion of carrier embryos will be a priority for those undertaking PGD to avoid passing on a serious single gene disorder. It is unclear whether there will be great demand by prospective parents undergoing PGD for the exclusion of healthy carrier embryos.

A relatively recent Australian study evaluated the social and moral concerns of patients presenting for PGD prior to initiating the treatment cycle.313 The study group consisted of three patient groups, one group presenting for PGD for single gene disorders, another group for aneuploidy screening and a control group who were about to commence their first IVF cycle. A questionnaire was administered individually and anonymously to each person. One part of the questionnaire dealt with issues surrounding selection and transfer of embryos as well as concerns in relation to knowledge of the carrier status of the embryo. The following question was posed:

If given the choice, would you accept the transfer of an embryo identified as being a healthy carrier?

In the group of couples presenting for PGD for single gene disorders, 63 per cent answered Yes, compared with only 8 per cent in the group presenting for aneuploidy screening and 22 per cent in the control group. The fact that those affected by the disorder in question were more willing to have a carrier embryo implanted in the hypothetical situation is significant. This may indicate a better understanding of carrier status on the part of the group presenting for PGD for single gene disorders.

Alternatively, it could mean that those not presenting for PGD for single gene disorders either did not understand carrier status or were more concerned not to pass on deleterious genes to subsequent generations. The authors of the study observed that:

Since half the subjects in this group are either asymptotic [sic] carriers themselves or have the indicated genetic condition, it is not surprising that they value their own genetic status.314

The majority of subjects (78 per cent) considered that the couple (after consultation with the doctor) should decide which embryos should be available for transfer.

The study was carried out in the Australian state of Victoria. At the time, performing PGD for single gene disorders was restricted to selection against affected embryos only. This was subject to the exception of female carrier embryos of an X-linked disorder in which some disease symptoms could manifest.315

Earlier studies have questioned whether there will be a wholesale uptake of PGD in general. One such study published in 1997 researched the attitudes to PGD of 245 people who were carriers of recessive disorders and at risk of having affected children (as opposed to carrier children). It found that despite support for PGD, natural conception followed by prenatal diagnosis remained the treatment of choice. Whilst the significant advantages of PGD were acknowledged, they were not sufficient to displace the reproductive option of prenatal diagnosis despite the difficulties associated with termination.316

A study of approximately half the New Zealand haemophiliac population carried out in the mid 1990s found very little enthusiasm even for prenatal testing.317 (PGD does not appear to have been discussed in the research, which focused on the options of amniocentesis or chorionic villus sampling.) This was because of the perceived link between a test revealing haemophilia and termination. This reluctance was partly based on the idea that ‘you took what you got’, but was also to avoid the expectation that termination should follow a positive result.318 Those who underwent prenatal testing did so mainly to prepare themselves for what lay ahead.

These studies may only be relevant for the particular period of time during which they were conducted. As PGD becomes more established and accessible, and people are reassured of the safety of the procedure, it may become a more realistic option for those who are at risk of transmitting serious heritable disorders. It has recently been reported that between 4 to 6 per cent of IVF carried out in the United States includes PGD. However, two-thirds of all cycles in 2005 were for aneuploidy screening.319 Some points may be extrapolated from the studies discussed.

The first is that not all people at risk of transmitting serious disorders will find PGD an acceptable option and engage in this technology. The second is that many people who are undergoing PGD for single gene disorders will be prepared to have an unaffected carrier embryo implanted if given a choice. Sometimes technologies such as prenatal diagnosis, which are presented as providing greater options to prospective parents, may not be experienced by those people as providing a real choice. In the context of prenatal diagnosis and developments in the ability to screen foetuses it has been observed that:

As ‘choices’ become available, they all too rapidly become compulsions to ‘choose’ the socially endorsed alternative. In this realm, it is amazing how quickly so-called options are transformed into obligations that, in fact, deprive us of choice.320

Accordingly, when considering the issue of unaffected carrier embryos, what is regarded as legally permissible must be distinguished from what is morally required. A related issue is that carrier status may not always be well understood. A prime example of this is a pilot genetic screening project which was carried out in Greece. The aim was to identify carriers of the gene that causes sickle cell disease. However, as a result of poor understanding, carriers were ‘stigmatised by their community and considered ineligible for marriage, except to other carriers’.321 As one commentator noted:

Few, if any of us, would choose to have a child who suffers from a genetic condition, but the impact of carrier status, as has already been seen, is poorly understood and may lead to the destruction of embryos based on the false belief that in some way they are ‘unhealthy’ or ‘defective’. 322

In Sweden, information is not provided to parents regarding the carrier status of embryos, regardless of the seriousness of the condition involved, on the grounds that carrier status will not adversely affect the prospective child. This stance seems to be predicated on the belief that society should not start selecting against unaffected carriers since everyone carries genetic mutations which do not necessarily affect them. Therefore ‘there is an unknown risk for everyone that the combination of one’s own genes with the genes of another carrier will result in a child with a recessive disorder’.323 It has been estimated that each individual person carries between 4 and 8 recessive deleterious genes.324

Yet, it has been argued that whilst all people are carriers and mostly unaware of the array of mutations in their genetic blueprint, this is vastly different from the situation where information is available regarding a specific genetic risk which, if it occurs, is serious. It is true that a couple who go through PGD will be aware of the possible risk that the child may be a carrier, and that the child is free to access that information when they wish to do so. However, it has been claimed that ‘in all other areas of life it is assumed that one should try to minimise risks and exposure to risk’.325

New Zealand Law Foundation Research Reports

Human Genome Research Project --- "Genes, Society and the Future: Volume I" [2007] NZLFRRp 3