Reproduction in the age of genomic medicine: the emergence, commercialisation and implications of preconception expanded carrier screening

关于基因遗传的想法有力地塑造了我们对家庭、健康和风险的共同理解，越来越多的人认为，许多疾病的原因都植根于基因和DNA。随着在线直接面向消费者的检测试剂盒（如23andMe）的广泛使用，人们越来越多地被鼓励使用遗传信息来回答有关其健康的问题。在生殖方面，全基因组测序技术正被用于为寻求生育子女的夫妇提供一种新的检测形式-扩大的携带者筛查（ECS）。这项测试可以告知夫妇他们在试图怀孕之前将遗传性遗传疾病传播给未来后代的潜在风险。这种所谓的“遗传相容性”测试只需要一个血液或唾液样本，以确定未来的父母是否携带任何错误的基因突变的相同副本，因此有风险将其传播给他们的孩子。虽然携带者筛查以前只用于某些遗传疾病风险增加的家庭和社区，如Tay Sachs，但扩大筛查可以同时测试许多遗传疾病，并可用于任何有能力负担的“健康夫妇”。ECS允许筛查数百种致病基因突变，其中许多疾病不一定是无法治愈或危及生命的，其预后可能不确定，例如遗传性耳聋或仅在生命后期发生的癌症。“最佳”怀孕或“无病儿童”的吸引力使ECS成为一种有说服力的创新，在社会和商业上都具有潜在的巨大影响。在英国，ECS目前由一系列商业公司和生育诊所“直接向消费者”提供，费用高达1600英镑。然而，虽然对环境信贷服务的需求正在加快，但人们对其实施情况及其引起的社会、经济、道德和政策问题知之甚少。迫切需要证据表明ECS如何与现有的孕前服务和筛查相结合，如何营销，如何或是否应该监管，可能使用它的夫妇的经验，以及它对个人和社会的影响。利用医学社会学，科学和技术研究，经验生物伦理学和政治经济学的专业知识开发，这个合作和跨学科的项目旨在调查ECS的出现，用于一般人群中的先入之见，及其更广泛的影响。与利益相关者、最终用户和英国著名慈善合作伙伴共同设计（Progress Educational Trust），该研究将探讨几个关键问题：ECS作为一种新的商业生殖产品出现的社会和经济过程是什么;为什么准父母选择购买这种测试，以及先入为主的ECS对他们的期望，生殖决定和经验的影响;幼儿保育服务的推广如何改变我们对严重疾病、健康/残疾儿童、生殖风险和“做一个负责任的父母”的看法;幼儿保育服务目前作为一种商业产品出售，在生殖保健的获得和公平方面有何后果; ECS的推出将如何改变现有的筛查计划，以及它对政策、监管和实践的影响？该研究将使用一系列方法来解决这些问题，包括：文献和政策文件以及利益相关者访谈的范围;系统地绘制ECS在英国的提供，商业化和营销;对没有遗传病家族史的夫妇进行定性访谈，他们已经使用或打算使用ECS;与ECS提供者进行访谈。一系列影响活动将侧重于为决策者和专业人员提供证据，并提高公众认识和辩论。

Ideas about genetic inheritance powerfully shape our shared understandings of family, health and risk and there is a growing popular belief that the causes of many diseases are rooted in genes and DNA. With online direct-to-consumer testing kits (such as 23andMe) becoming widely available, individuals are increasingly encouraged to use genetic information to answer questions about their health. In the context of reproduction, genome-wide sequencing techniques are being used to provide a new form of testing - expanded carrier screening (ECS) - for couples who seek to have children. This test can inform couples about their potential risk of transmitting inherited genetic disorders to future offspring before trying to conceive. This so-called 'genetic compatibility' test requires only a blood or saliva sample to determine if future parents carry the same copy of any faulty genetic mutation and are therefore at risk of transmitting it to their children. While carrier screening was previously only used among families and communities who were at increased risk of certain genetic conditions such as Tay Sachs, expanded screening can test for many inherited conditions simultaneously and is available to any 'healthy couple' who have the means to afford it. ECS allows screening for hundreds of disease-causing genetic mutations, many of which are not necessarily incurable or life-threatening and whose prognosis may be uncertain, such as inherited deafness or cancers which only occur late in life. The allure of an 'optimal' pregnancy or 'disease free child' makes ECS a persuasive innovation with potentially considerable impact both socially and commercially. In the UK, ECS is currently being offered 'direct to consumer' by a range of commercial companies and fertility clinics at a cost of up to £1600. However, while demand for ECS is gathering pace, little is known about its implementation and the social, economic, ethical and policy questions it raises. Evidence is urgently required about how ECS interfaces with existing preconception services and screening, how it is marketed, how or if it should be regulated, the experiences of couples who might use it, and its implications for individuals and society. Developed using expertise in medical sociology, science and technology studies, empirical bioethics and political economy, this collaborative and interdisciplinary project aims to investigate the emergence of ECS for preconception use amongst the general population, and its wider implications. Co-designed with stakeholders, end users and a prominent UK charity partner (Progress Educational Trust), the study will explore several key questions: what are the social and economic processes at play in the emergence of ECS as a new commercial reproductive product; why do prospective parents choose to buy this test and what is the impact of preconception ECS on their expectations, reproductive decisions and experiences; how is the diffusion of ECS reshaping how we think about severe diseases, healthy/disabled children, reproductive risks and 'being a responsible parent'; what are the consequences of ECS being currently sold as a commercial product in terms of access and equity in reproductive healthcare; how will the roll out of ECS transform existing screening programmes and what are its implications for policy, regulation and practice? The study will use a range of methodologies to address these questions including: scoping of literature and policy documents and stakeholder interviews; systematically mapping the provision, commercialisation and marketing of ECS in the UK; qualitative interviews with couples with no family history of genetic conditions who have used or intend to use ECS; and interviews with ECS providers. A range of impact activities will focus on providing evidence for policymakers and professionals and on raising public awareness and debate.