Gene Editing in Aotearoa – Legal Considerations for Policy Makers

Gene editing use in pest control, primary industries and human health care pose significant new challenges for regulation. Under current New Zealand legislation (the Hazardous Substances and New Organisms Act 1996) and a judicial ruling on interpretation of the legislation and regulations, the status of gene edited organisms in New Zealand are considered genetically modified and are regulated as new organisms employing a precautionary approach. This article has identified some of the complexities of the legislation inherent in regulating a rapidly developing technology, where such advances may be well ahead of current frameworks and public acceptance. Legal and policy issues have been considered. A future-proof framework to keep abreast rapidly advancing biotechnologies is required whereby new legislation for biotechnologies is developed and a single-entry point for biotechnology applications is implemented. Most importantly this article recommends valuing Treaty of Waitangi principles and have those principles lead us in all that we do.&nbsp

Conclusions and Recommendations

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. 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. 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. 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. Firstly, 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

Main Findings

Preimplantation genetic diagnosis (PGD) is publicly funded in New Zealand from 2006. PGD poses a range of issues that have ongoing significance for other later emerging applications of genetic technologies arising from the sequencing of the human genome. The idea of the ‘designer baby’ is the most publicly proclaimed outcome of new developments in genetic medicine

Genetic Testing and Microarray Technologies

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

New Possibilities for Newborn Genetic Screening: Screening for Genetic Susceptibility to Common Disease

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. Three mother-baby cohorts are studied: 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. 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

Researching Human Genetic Variation: An Examination of the Ethics of Genetic Research

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 breakthroughs 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. An ethical protocol is set out here 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. Researchers should 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

Introduction

Abstract for all parts of Volume II: 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. 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 counseling, if required. 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. 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. Firstly, 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 counseling 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

Benefits and Harms in Genetic Testing of Minors

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. 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. 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. 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. Firstly, 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

Newborn Screening: Present and Future

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. More public education and information regarding the programme, particularly in antenatal classes and on the internet, should 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. 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 coordination initiatives; though, equally, the programme legitimately belongs within the mandate of screening services. 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. 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, should be reformulated for newborn screening