In Chapter 12, the techniques used for editing genomes are discussed, from early gene targeting approaches to highly specific CRISPR and prime editing techniques using engineered nucleases. The development of techniques through zinc-finger nucleases and TALENs is used to set the context for the CRISPR and prime editing methods that have become widely accessible and are used extensively to make changes to genomes. As an alternative to editing the genome, RNA editing offers a different approach that enables modulation of gene expression without complete inactivation or alteration of genes and may be more appropriate in some therapeutic situations. The potential for genome and RNA editing is outlined, and the ethical aspects noted.

Medical and forensic applications of recombinant DNA are described in Chapter 15. The range of genetically based diseases is outlined, and potential therapies discussed, covering diagnosis of infection, comparative genomics, development of vaccines, therapeutic antibodies and xenotransplantation. Treatment using gene therapy approaches is described, and the relatively limited success of gene therapy is considered in the context of its initial promise and the expectations that emerged from this. RNA-based therapies are covered by discussing RNA interference and antisense oligonucleotides, and the medical applications of genome editing are considered. The CCR5 controversy, known as the ‘CRISPR babies scandal’, is mentioned as an example of how the overall system can fail to prevent unethical practices when these are driven by determined scientists and clinicians. DNA profiling for analysis of DNA is described, and its use in forensic, legal and other applications is outlined.

This chapter analyzes the technology of human genome editing with a focus on the ethical issues involved and offers guidance as how best to regulate this technology. First, this chapter explains several common types of gene editing technologies and then analyzes the ethical implications of the two primary therapeutic uses of gene editing: somatic and germline. Primary ethical analysis will focus on the bioethical principles of autonomy, beneficence, non-maleficence, and social justice; analysis will then provide a weighing of these principles and likely consequences–noting the biologic differences between somatic versus germline treatments. Somatic gene editing is generally more confined to the individual, while germline editing changes the genes of cells that are passed sexually to offspring, thus having the power to shape the human genome generationally--the ultimate consequence of which is the influence and shaping of human evolution. In conclusion, the chapter argues the consequences of somatic vs. germline genome editing demand that, when considering the proper emphasis of a regulatory paradigm, somatic editing should be regulated under a nationally guided framework and germline editing should be regulated under both a nationally and globally guided framework.

Genetic testing and gene editing are rapidly becoming – indeed, already are – consumer Genetic testing and gene editing are rapidly becoming – indeed, already are – consumer technologies that people can experiment with and apply on their own, potentially without any involvement by traditional payers and research funding agencies, professional scientists and healthcare providers, regulators, and medical product manufacturers. This chapter explores the challenges of regulating direct-to-consumer and do-it-yourself genomic technologies that disrupt the traditional funding, supply arrangements, and roles. It is widely understood that the U.S. Coordinated Framework for biotechnology regulation, even after a 2017 update, is a patchwork of old federal statutes that were never designed for some of the genetic technologies now emerging. This chapter explores four problems that are less well understood: First, consumer genetics poses a fundamental challenge, also seen in the sharing economy exemplified by ride-sharing platforms such as Uber and Lyft. This challenge is one of scale, and the need for regulators to oversee a massive number of small-scale transactions and individual actors. A second challenge is that consumer genetics forces a rethinking of the goals of regulation – specifically, how paternalistic is it appropriate for regulators to be? A third conundrum is whether top-down regulatory approaches can be effective and, if not, how to motivate bottom-up, citizen-led norm-setting and compliance. A final challenge concerns the fact that the human genome itself is, ultimately, software, and many of the consumer products for interpreting and manipulating it also are in the nature of software, yet traditional consumer safety regulators struggle when confronted with the task of regulating software. The chapter concludes that merely expanding the jurisdiction of existing regulatory bodies and granting them new tools and powers will not suffice. A more sweeping redesign of consumer safety regulation will be required.

Human germline genetic modification (HGGM) has been the subject of bioethical attention for over four decades. Recently, however, two areas of biomedical technology have revived debates over HGGM. The current ‘regulatory moment’ with respect to HGGM thus perhaps represents something of a watershed for the global governance of science more generally. This chapter considers broader lessons we might learn from examining the challenges of HGGM for the future of health research regulation. HGGM, I suggest, is a contemporary global regulatory experiment-in-progress through which we can re-imagine the regulation of (in particular, ethically contentious) science and innovation: what it should address, what its purposes might be, and how, therefore, we should go about shaping global scientific regulation. Through examining this, I argue that such regulation should focus on processes and practices, rather than objects; and that its utility lies more in mediating these processes than in establishing absolute prohibitions or bright lines.

Australia was at the cutting edge in the development of Artificial Reproductive Technology in the 1960s and 1970s. Regulatory responses were piecemeal: only a small number of the six states and two territories enacted legislation. The regulatory response to reproductive cloning and embryonic stem cell research has been more uniform, with nationally consistent legislation in the form of the Prohibition of Human Cloning for Reproduction Act 2002 and the Research Involving Human Embryos Act 2002, together with the Gene Technology Act 2000. This regulatory regime creates a prohibitory environment for germline genome therapy in Australia and provides little scope for genome editing research involving human embryos, even under licence. This chapter discusses the Australian regulatory regime, with particular focus on this triad of legislative instruments. Although Australia has made a commitment to science and health, and recognition of the right to found a family, the special status of the embryo is a paramount consideration. This chapter concludes that, as in many other countries, Australia is at a crossroads, and Australians must decide, collectively, how far genome editing research involving human embryos should be allowed to progress.

This chapter offers a paramount analysis of Spain’s regulatory framework for human gene editing. This is a particularly complex task, due to several reasons. First, Spain not only ratified the Oviedo Convention, which rules gene editing, but has also developed a national legal framework that sometimes contradicts it. Second, many competencies related to monitoring and control have been developed at the regional level to “autonomous communities” (Comunidades Autónomas). In general, the Spanish response to the issues posed by human gene editing can be summarized like this: somatic gene editing is perfectly acceptable, once the corresponding administrative steps are taken. Germline gene editing, instead, is illegal provided that it affects someone's descendants. The legal stature of basic science involving germline gene editing remains unclear. The final decision should be adopted in a case-by-case analysis by corresponding ethics committees.

In France, civil law provisions on research involving human subjects, on donation and use of human body parts, and on medically assisted reproduction – originally developed between 1988 and 1994 and generally referred to as loi de bioéthique (law on bioethics) – specify whether and under which statutory conditions activities potentially leading to human germline genome modification can be undertaken. International law, including European law, poses further conditions. This chapter explores legislative and regulatory constraints on this type of research in France, analyzing how they developed over time to reach their present state. We will show that, in France, it is prohibited to create a human embryo solely for research purposes; that, however, research activities on supernumerary embryos and human embryonic stem cells are possible upon authorization by the national agency on biomedicine; but that, nevertheless, alterations to the genome of an embryo under circumstances that allow the modifications to pass on to future generations (i.e. through a successful pregnancy) are strictly prohibited. A peculiar feature of French legislation in this domain is that the law on bioethics is regularly updated in light of new technological or scientific developments, and as a result of a national public consultation held at least every five years. In 2018 one such rounds of public consultation took place, and a report summarizing its outcome is now being considered as the basis for possible legislative reform – including in the domain of genetic engineering. While it is not possible to anticipate future legislative developments, the report signals some degree of openness in the French civil society regarding the use of genetic engineering and genome editing, at least in the context of research.

The use of genetic technologies for reproductive, farming, agricultural and scientific purposes has long been a matter of public concern in Switzerland. As a result of a series of legislative initiatives at the federal level, as well as of popular referenda, the country developed one of the most restrictive regulatory environments in Europe for research, potentially leading to human germline genome modification. In particular, any genetic manipulation of reproductive cells or embryos is strictly forbidden, regardless its intended purpose. This chapter will illustrate the way constitutional- and federal-level legislation, as well as international law and regulatory provisions rigidly constrain research activities that could potentially lead to genetic alterations in humans and their progeny. In such a restrictive context, it is highly unlikely that recent technical advances in genetic engineering and genome editing will be employed to produce germline genome modifications for either medical or purely scientific purposes. Furthermore, while the Swiss National Advisory Commission for Biomedical Ethics has recently expressed partial support for basic research possibly involving the genetic modification of human embryos, there are currently no indications that legislative initiatives will be undertaken to ease current regulations on such controversial matters.

Belgium regulates research on human embryos, including germline modification, mainly through the 2003 Law regarding Research on Embryos In Vitro and the 2007 Law regarding Medically Assisted Reproduction and the Disposition of Embryos and Gametes. It allows the creation of embryos for research when the research goal cannot be reached by research on supernumerary embryos. The lawmaker only recognizes a gradual difference between embryos created for reproduction and later used for research and embryos specifically created for research purposes. The general rule in research is that no research can be performed for eugenic goals, i.e., selection or improvement of non-pathological characteristics of the human species. Everything that is not prohibited by the law is allowed. The conclusion, supported by the parliamentary debate, is that germline genome editing is permitted for corrective purposes (meaning elimination or correction of genetic diseases), if approval of the local ethics committee and the Federal Commission on scientific research on embryos in vitro is obtained.