Martina C. Cornel

The interface between assisted reproductive technologies and genetics: technical, social, ethical and legal issues

The interface between assisted reproductive technologies (ART) and genetics comprises several sensitive and important issues that affect infertile couples, families with severe genetic diseases, potential children, professionals in ART and genetics, health care, researchers and the society in general. Genetic causes have a considerable involvement in infertility. Genetic conditions may also be transmitted to the offspring and hence create transgenerational infertility or other serious health problems. Several studies also suggest a slightly elevated risk of birth defects in children born following ART. Preimplantation genetic diagnosis (PGD) has become widely practiced throughout the world for various medical indications, but its limits are being debated. The attitudes towards ART and PGD vary substantially within Europe. The purpose of the present paper was to outline a framework for development of guidelines to be issued jointly by European Society of Human Genetics and European Society of Human Reproduction and Embryology for the interface between genetics and ART. Technical, social, ethical and legal issues of ART and genetics will be reviewed.

Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 1 - From blood spot to screening result

In many European countries neonatal screening has been introduced over the last 50xa0years as an important public health programme. Depending on health care structure, available funds, local politics, input from professional groups, parent groups, and the general public this introduction has led to different approaches in the way the screening programmes have been set up, financed and governed. To get some insight about the current situation, in 2009 the European Union, via its EAHC agency, put out a call for a tender that was acquired by our project group. An online survey was compiled in which the whole screening programme was covered by a questionnaire. This survey covered the EU member states, (potential) candidate member states and EFTA countries, in total 40 countries. Results showed little consensus concerning 1. information of parents including informed consent; 2. which conditions are screened for, ranging from 1 to around 30 conditions; 3. sampling time post partum; 4. screening methodology including cut-offs values even between screening laboratories within countries.; 5. storage of residual specimens, varying from 3xa0months to 1000 years. In addition, confirmatory diagnostics and follow-up also show large discrepancies (Burgard et al. http://www.iss.it/cnmr/prog/cont.php?id=1621&lang=1&tipo=64 2011). In addition to the current practices report an expert opinion document has been produced with recommendations to the EU Commission for future improvements, e.g. in parallel to the way the USA has harmonized its practices based on recommendations by the American College of Medical Genetics (Watson et al., Pediatrics 117: S296-S307, 2006).

Towards a European consensus for reporting incidental findings during clinical NGS testing

In 2013, the American College of Medical Genetics (ACMG) examined the issue of incidental findings in whole exome and whole genome sequencing, and introduced recommendations to search for, evaluate and report medically actionable variants in a set of 56 genes. At a debate held during the 2014 European Society for Human Genetics Conference (ESHG) in Milan, Italy, the first author of that paper presented this view in a debate session that did not end with a conclusive vote from the mainly European audience for or against reporting back actionable incidental findings. In this meeting report, we elaborate on the discussions held during a special meeting hosted at the ESHG in 2013 from posing the question ‘How to reach a (European) consensus on reporting incidental findings and unclassified variants in diagnostic next generation sequencing’. We ask whether an European consensus exists on the reporting of incidental findings in genome diagnostics, and present a series of key issues that require discussion at both a national and European level in order to develop recommendations for handling incidental findings and unclassified variants in line with the legal and cultural particularities of individual European member states.

Developing a policy for paediatric biobanks: principles for good practice.

The participation of minors in biobank research can offer great benefits for science and health care. However, as minors are a vulnerable population they are also in need of adequate protective measures when they are enrolled in research. Research using biobanked biological samples from children poses additional ethical issues to those raised by research using adult biobanks. For example, small children have only limited capacity, if any, to understand the meaning and implications of the research and to give a documented agreement to it. Older minors are gradually acquiring this capacity. We describe principles for good practice related to the inclusion of minors in biobank research, focusing on issues related to benefits and subsidiarity, consent, proportionality and return of results. Some of these issues are currently heavily debated, and we conclude by providing principles for good practice for policy makers of biobanks, researchers and anyone involved in dealing with stored tissue samples from children. Actual implementation of the principles will vary according to different jurisdictions.

Genetic testing and common disorders in a public health framework: how to assess relevance and possibilities

Genetic testing and common disorders in a public health framework: how to assess relevance and possibilities

The Dutch national summit on preconception care: a summary of definitions, evidence and recommendations.

In conclusion, a consensus was achieved on the majority of the key elements of PCC, including the definition, the categorisation, institutes and health care professionals which should play a role in reaching target groups, the content and delivery and the need for development of evidence-based risk assessment instruments. These elements give further insight in what should be resolved in order to enlarge the scale at which PCC is delivered. Furthermore, these can be used as starting points for policymakers and other relevant actors that take responsibility to develop implementation strategies for PCC. n nIn order to develop a tailored PCC programme, the needs of specific populations should be known and resources should be in line with setting specific characteristics. n nThis consensus paper is based on current evidence. Biannual update on the evidence of preconception risk factors and management is recommended to keep the debate going. This debate is necessary to hold the commitment amongst the broad scope of professionals in the curative setting and the public health care setting to collaborate regarding PCC.

Governing biological material at the intersection of care and research: the use of dried blood spots for biobanking

A series of governance issues currently surrounds the multiple uses and multiple users of dried blood spots (DBS) for research purposes. Internationally there is a discussion on storing DBS resulting from newborn screening for public health and using them as the basis for large biobank-like collections to facilitate biomedical research. If such a transformation were to be formalized, then DBS would sit at the intersection of care (ie, public health) and research, with the mechanisms through which such a collection could be managed not totally self-evident. What is more, a DBS collection raises questions about the fuzzy boundaries between privacy and anonymity; how to control or define quality control uses of DBS; medical vs nonmedical uses; as well as benefit sharing and stakeholder involvement. Our goal here is to explore some of the key questions relating to DBS governance by way of the bio-objects and bio-objectification concepts. By embracing – rather than resisting to – the blurring of boundaries and problems in categorization that have come to characterize bio-objects and bio-objectification processes recently described in this journal, we attempt to highlight some issues that might not be currently considered, and to point to some possible directions to go (or avoid). Building from our knowledge of the current DBS situation in the Netherlands, we outline questions concerning the uses, management, collection, and storage of DBS.

Renal defects and limb deficiencies in 197 infants: Is it possible to define the "acrorenal syndrome"?

Dieker and Opitz in 1969 described the simultaneous occurrence of limb deficiencies (LDs) and renal anomalies (RAs) in three patients. Curran and Curran introduced in 1972 the term “acrorenal syndrome.” Since then, the term “acrorenal syndrome” is used occasionally, but a well‐circumscribed definition has never been established. On the other hand, the concept of an acrorenal polytopic developmental field defect was postulated by Opitz and others to explain the association between RAs and LDs. We undertook this study to investigate whether this acrorenal “syndrome” could be identified in a large group of cases with congenital RAs and a limb deficiency. Eleven birth defect registries that are part of the International Clearinghouse for Birth Defects Monitoring (i.e., registries of ICBDMS in Finland, France [Paris and Strasbourg], Israel, Italy [IPIMC and Emilia Romagna], Mexico, Northern Netherlands, South America, Spain, and the United States [Atlanta]) provided data on 815 infants who had a LD and at least one other major congenital anomaly. These 815 cases were ascertained among 5,163,958 births. We selected the 197 cases who had both a limb deficiency and a renal or urinary tract anomaly. In about 50% of these cases a diagnosis or a recognized phenotype was reported, with chromosomal aberrations and VACTERL being most frequent. In the group with no diagnosis or recognized phenotype (95 cases), we looked for (a) clustering of specific types of LDs and RAs, and (b) for clustering of associated anomalies, in order to find evidence for and be able to define better the term “acrorenal syndrome.” Our data suggest that an association exists between LDs and RAs, possibly explained by the concept of the acrorenal polytopic developmental field defect. However, our dataset does not yield evidence for the existence of one distinct “syndrome,” defined as a pattern of causally related multiple anomalies. Therefore, use of the term “acrorenal syndrome” should be avoided.

Improving test properties for neonatal cystic fibrosis screening in the Netherlands before the nationwide start by May 1st 2011

When new technical possibilities arise in health care, often attunement is needed between different actors from the perspectives of research, health care providers, patients, ethics and policy. For cystic fibrosis (CF) such a process of attunement in the Netherlands started in a committee of the Health Council on neonatal screening in 2005. In the balancing of pros and cons according to Wilson and Jungner criteria, the advantages for the CF patient were considered clear, even though CF remains a severe health problem with treatment. Nevertheless, screening was not started then, mainly since the specificity of the tests available at that time was considered too low. Many healthy infants would have been referred for sweat testing and much uncertainty would arise in their parents. Also the limited sensitivity for immigrants and the detection of less severe phenotypes and carriers were considered problematic. The Health Council recommended a pilot screening project which was subsequently performed in some provinces, leading to a 4-step protocol: IRT, PAP, screening for a CFTR mutation panel, and sequencing of the CFTR gene. This would lead to the identification of 23 cases of classical CF, two infants with less severe forms and 12 carriers per year in the Netherlands. Thus many CF patients can be diagnosed early, while limiting the number of referrals, the number of infants with less severe forms diagnosed and the number of carriers identified. Technical solutions were found to limit the ethical problems. A nationwide program using this four step protocol started by 1 May 2011.

GenEthics and religion

Based on the symposium ‘GenEthics and Religion’ held in Basel, Switzerland, in May 2008, this volume examines the role religion can play in establishing ethical guidelines to protect human life in the face of rapid advances in biology and especially gene technology. Book contributions were written by philosophers, theologians, human geneticists and several bioethicists representing the Christian, Jewish, Islamic and Buddhist perspectives. n nProgress in modern genetics challenges medical ethics. Religion and science are by no means totally separate from each other, although a certain distance has developed between theologians and scientists. Many theologians, however, show a distinctive interest in natural sciences, such as the Augustinian monk Gregor Mendel, the founder of modern genetics. A scientist’s daily work involves a profound and close study of creation which permits him a very direct insight into its ‘wonders’ and helps him develop great respect for its power. Interdisciplinary collaboration can be especially helpful in formulating guidelines for complex but concrete ethical issues. In medical genetics in particular, the counselling offered to patients often does not focus on scientific or medical aspects of a hereditary disease but rather on its ethical and psychosocial implications. Whilst basic principles of bioethics, such as autonomy, beneficence, non-maleficence and justice, as formulated by Beauchamp and Childress, play an important role in genetic health care, it is especially the interdisciplinary debate on practical questions related to prenatal diagnosis, pre-implantation diagnostics, genetic screening or synthetic biology that is needed to generate guidance in these new and challenging issues. This volume contributes to this interdisciplinary debate. n nThe book covers a wide range of topics and perspectives. I selected a few that caught my attention. The terminology used by journalists and scientists is full of metaphors. Using descriptions as the genetic blueprint for human beings may suggest that DNA contains the instructions for the body on how to develop, how to stay alive, how to grow, etc. Nowadays, the genetic determinism implied in the metaphor is not supported by most scientists, so a new metaphor is suggested by Rehmann-Sutter: systems. In complex molecular systems, mutual influences exist. Genes alone are not sufficient for the complete description of developmental pathways. Rather than considering nature responsible for writing our book of life, individual persons have a responsibility to know about their risk and possible precautions. n nThe Jewish perspective on genetics shows a striking paradox. No religious group has been more victimized by genetics than Jews, under the Nazi regime. Yet, no single religious group has been more receptive to genetic medicine than Jews, including prenatal testing, in vitro fertilization, pre-implantation genetic diagnosis, preconceptional screening and stem cells. At its roots, Judaism is a tradition that sees human beings as ‘co-creators’ with God in creation and that does not exhibit a fear that human beings will use technology to ‘play God’. n nThe Muslim perspective is described by Siti Nurani Mohamed Nor. As Asia is the hub of biotechnological superpowers, Nor’s chapter is focussing on biotechnology, especially human embryo research. According to her, there is a plurality of views regarding the beginning of life. Lawmakers consider every action in light of the choice of the lesser of two evils, in this context foregoing the potential of gene technology vs. infringements of the objectives of Islamic law, which are defined by five basic human interests: life, religion, property, intellect and family lineage. On the beginning of human life, there is a general consensus that there is potential life in early embryos and they must be treated with caution. The intention to eliminate diseases may be justified in actions that may bring about the possibility of embryo destruction. This sometimes is interpreted to be the lesser of two evils. She further proposes a reasoned and sustained deliberation on the ethics of stem cell research, including biotechnological as well as philosophical and theological perspectives. n nBuddhism, according to Pinit Ratanakul, in principle has no difficulty to cope with new scientific achievements such as genetics and biotechnology. Advances in human genetic research and its applications in medical practices such as diagnosis, treatment and prevention of genetic diseases are of great promise and bring hopes for the cure of incurable diseases which many people are afflicted with. The core of Buddhist ethics is compassion, involving beneficence, non-maleficence and other forms of altruism. Buddhism sees the Human Genome Project and genetic engineering technologies as important ways to relieve human suffering and promote human well-being. The reason for this liberal attitude of Buddhist ethics towards genetics is to be found in a general affinity of Buddhism and science as both see the need for the verification of truth by reason and experience. A less liberal attitude applies to the beginning of life. An embryo is human and thus possesses human dignity and human rights at the time of conception. In Buddhism, persons are interdependent. Germline cell therapy for instance is ethically questionable due to its potentially negative effects on humanity. n nFive parts and 13 chapters contain a diversity of issues for debate. In pluralistic societies and within several religious groups, discussions on how to balance pros and cons of genetics and biotechnology are taking place. The book presents a kaleidoscope of these perspectives and shows that the challenges of the rapid progress of modern gene technology demand that religious ethics engages in new ideas and unorthodox ethical reflections.