22 JANUARY 2016 • VOL 351 ISSUE 6271 337 SCIENCE sciencemag.org By R. Isasi, 1,2 * E. Kleiderman, 2 B. M. Knoppers 2 B alancing therapeutic prospects brought by scientific advances with regulation to address highly con- tested socioethical issues is the ul- timate challenge in dealing with disruptive science. Human genome editing is a powerful tool that offers great scientific and therapeutic potential (1, 2). Yet, it rejuvenates socioethical and policy questions surrounding the acceptability of germline modification. The first national research application for licensing genome editing in hu- man embryos is about to be filed in the United Kingdom (3). This is a country offering robust oversight, while also adopting a bold approach toward in- novative science. At the same time, a revised pan-European regulation on clinical trials will come into effect in May of 2016 that would continue a prohibition on carrying out gene therapy clinical trials that “result in modifications to the subject’s germ line genetic identity” (4). “Genetic identity,” how- ever, has yet to be defined, and we need to look for an approach to genome editing that can lead toward compromise or consensus. Defining the contours and diversity of national policy frameworks governing the human germ line is difficult. The permissi- bility of conducting research on clinical ap- plications of genome editing on early human development is often considered part of the regulatory approaches to assisted human reproductive technologies, stem cells, or ge- nomic research. Similarities and differences between approaches also need to be consid- ered. Internationally, policies extend across a continuum that distinguishes between de- grees of permissiveness, that is, between le- gally binding legislation and regulatory and/ or professional guidance or research versus clinical applications. We drew on a repre- sentative sample of 16 countries to provide a global ”snapshot” of the spectrum of policy and legislative approaches (restrictive to per- missive) regarding human germline editing, human embryonic stem cell research, hu- man reproductive cloning, human research cloning, human somatic gene therapy, and pre-implantation genetic diagnosis (see the figure). Our sample also represents countries in which innovative research in the fields of genomics and stem cells is being carried out and/or that are hot spots for stem cell and re- productive tourism. For each technology, we showed whether it is being governed by laws (legislation) or by normative documents and policies (regulatory). Where legislation has been adopted either prohibiting or restricting germline interven- tions, it is mostly accompanied by criminal sanctions ranging from hefty imprisonment terms to fines (e.g., Australia, Belgium, Bra- zil, Canada, France, Germany, Israel, Nether- lands, and United Kingdom). However, such restrictive legislation frequently requires that there be intentionality on the part of the in- dividual (mens rea). For example, legislation adopted in Australia targets the intentional alteration of “the genome of a human cell in such a way that the alteration is heritable by descendants or the human whose cell was altered” (5, 6). It further criminalizes in- tentionally placing “an embryo in the body of a woman knowing that, or reckless as to whether, the embryo is a prohibited em- bryo.” Under Australian law, an embryo with an altered germ line or an embryo created solely for research purposes is considered a “prohibited embryo” (5, 6). The intentional- ity provision has created a degree of policy uncertainty, particularly in terms of down- stream restrictions on certain applications, such as clinical uses. Restrictive policy approaches also usually include upstream limitations, which outlaw a technology or an application regardless of its purpose by means of tight regulations, blan- ket prohibitions, or moratoria. These types of restrictions are exemplified in broad, bottom- up bans on human embryo and/or germline manipulations, embryo genetic testing, and somatic cell nuclear transfer technologies. Germany and Canada have adopted up- stream criminal bans on germline interven- tions and also restrict embryo research. Nonetheless, some enacted prohibitions can be rendered ineffective or inadequate in practice, such as when the scope of laws fo- cuses on a particular technology that is later outpaced by scientific developments. Simi- larly, prohibitions will be limited if exceptions are allowed. This is the case for provisions that, although aiming to adopt a restrictive approach toward embryo research, allow for interventions deemed therapeutically benefi- cial to the embryo or necessary for the pres- ervation of its life, or are required in order to achieve a pregnancy (e.g., Belgium, Germany, and France). The vague language of such pro- visions means they would become obsolete once the particular intervention is consid- ered standard clinical practice (7, 8). Legal uncertainty comes into play when dealing with medical innovation. Finally, restrictive policies signal a criti- cal attitude toward science because of fears of commodification of potential human life, and they advocate for strong government in- tervention in the regulation of research. The most frequent approach is intermedi- ate. Hereunder, the application of genomic technologies in embryos and germ cells is al- lowed but closely monitored by governments (8) with the goal of providing efficient and safe mechanisms for conducting research. In the context of genome editing, a particular technology or an intervention is not banned per se. Rather, specific downstream applica- tions are forbidden, such as attempting to initiate a human pregnancy with an embryo or a reproductive cell whose germ line has been intentionally altered (e.g., France, Israel, Japan, and Netherlands). In sum, reproduc- tive purposes are typically outlawed, whereas scientific research activities, such as investi- gating basic biology or aspects of the method- ology itself are generally permitted. A few countries have permissive ap- proaches that aim to promote scientific progress with the belief that it is beneficial for humanity. Here, a wide range of activi- ties are permitted, provided that governance is observed, mostly by means of de facto or case-by-case approval by a licensing author- ity. Illustrative examples of this approach are found in policies adopted in the United Kingdom and China, where conducting re- search for reproductive purposes is permit- ted and potential clinical applications are not GENETIC TECHNOLOGY REGULATION Editing policy to fit the genome? Framing genome editing policy requires setting thresholds of acceptability “the thresholds the PGD model delineates…represent a robust approach to regulation.” POLICY 1 Dr. John T. MacDonald Foundation Department of Human Genetics, University of Miami, Miami, FL 33136, USA. 2 Centre of Genomics and Policy, Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, Quebec H3A 1A4, Canada. *Corresponding author. E-mail: rosario.isasi@icloud.com Published by AAAS on January 29, 2016 Downloaded from on January 29, 2016 Downloaded from on January 29, 2016 Downloaded from