This news piece in Nature reflects on recent developments in embryo research to point to the gap between the pace of scientific research and the abilities of regulatory institutions to keep up with new developments. It draws on the He Jiankui affair and the International Summits on Human Genome Editing as other examples of this problem. The author argues that the ideal solution is an agile regulatory process that can quickly respond to new developments while also being receptive to input from experts and non-experts alike.
May 10, 2023In a recent article focusing on the regulatory challenges posed by new development in embryo research, the Global Observatory is mentioned as one effort rethinking the relationship between regulatory limits and the pace of scientific research.
The Human Fertilisation and Embryology Act was passed in British Parliament in 1990 and has since become a model of the regulation of human reproductive technologies. The legislation sought to maintain the status of the human embryo reached through deliberations in the previous decade, taking into account the 1987 white paper “Human Fertilisation and Embryology: a Framework for Legislation” and the 1984 Warnock Report (see Michael Mulkay  for an account of the events between the Warnock Report’s release and its enshrinement into law).
This article in The CRISPR Journal represents an extensive survey of 106 nations regarding their policies on early-stage embryo genome editing research. It is the product of a collaboration between bioethicists at Dalhousie University and members of the Center for Genetics and Society. The authors argue that international policies about heritable genome editing were previously underreported. Their findings suggest that there is indeed some global consensus around the prohibition of heritable human genome editing.
This report follows the recommendation of the Warnock Report (1984) in creating an independent government body to regulate and oversee assisted reproduction. In the following years, given the diversity of views on the subject, the government made a series of public consultations. By the time the consultation period ended in June 1987, the British Government reaffirmed its intention to have legislation on assisted reproduction, a task for the British parliament.
This is one of two articles published on the same day in the Guardian that suggests an emerging strategy to modify the UK’s Human Fertilisation and Embryology Act. This article identifies recent developments in life science research—specifically, genome editing, synthetic embryos, mitochondrial transfer, and lab-grown gametes—and suggests that revisions to the 1990 Act would need to account for progress in these areas. The article argues that scientific progress in each of these domains necessitates “future-proofing” legislation so that these technologies can be translated into the clinic.
Following a UNESCO meeting in Paris, the International Bioethics Committee (IBC) released this report, which clarifies its stance on recent research related to human genomics. It includes special considerations for heritable genome editing and specifically calls for a moratorium on such applications. The reasoning the IBC provides is that such interventions raise “serious concerns,” including threats to human dignity and the prospect of eugenic applications.
This treaty is more commonly known as the “Oviedo Convention,” after the city in Spain where it was ratified. The Oviedo Convention is based on the European Convention of Human rights and is the only legally binding international instrument for protecting human rights in biology and medicine, covering both clinical and research settings and giving special consideration to human dignity. It lays out the rights of patients and research subjects for Europe, focusing largely on individual rights of informed consent and privacy but also mandating consideration of equitable access to health care.
The authors, some of whom are ISSCR affiliates involved in the production of the 2021 guidelines, provide an overview of topics that were updated in the guidelines (chimeric embryos, mitochondrial replacement techniques, stem cell-based embryo models). They make the case that relaxing research in these arenas has great potential for medicine science. To realize such benefits, they call for a reform of research oversight policies worldwide, within ethical acceptability, as the updated guidelines of ISSCR propose.
In this commentary, the authors argue that it is time to consider if the 14-day rule can be extended to 28 days. They provide a list of arguments in favor of such an extension, including the opportunities to open up the “blackbox” of embryo development, increased knowledge about embryonic development and improvement of IVF procedures and the study of “synthetic” or stem cell-based embryos. Regarding ethical reasoning for the 14-day rule, they make several arguments.
Bioethicist Françoise Baylis draws attention to the revised 2021 ISSCR guidelines for stem cell research and clinical translation, for leaving open the question of the permissibility of human genome editing. For Baylis, the “review categories” of the guidelines are ambiguous on whether heritable human genome editing would be allowed.
The authors respond to McCully’s (2021) arguments for extending the 14-day rule to 28 days. They argue that biomedical advances do not justify changing the rule, since the reasoning of the Warnock Committee remains relevant. The authors maintain their defense of the 14-day rule on the following grounds: 1. The Warnock Committee reasoning was based on maintaining public trust and providing a moral justification for using embryos, concerns that have not changed to date; 2. Extending the 14-day rule would justify previous concerns about a slippery slope; 3.
The author analyzes the main justifications provided by the Warnock committee for the 14-day limit of embryo research in vitro and finds them unconvincing; discussions about extending the limit must determine whether the limit was valid in the first place. The first objection is against the argument that individuation is necessary for moral status, since it can occur later than 14 days, and an individual entity is present before any twinning.
This article explores the main arguments in favor of and against extending the 14-day limit for conducting research on human embryos. Cavaliere also provides an overview of the historical roots of the 14-day rule and notes that it favored compromise between competing moral views. For the author, the potential research benefits of keeping embryos alive for longer than ever before do not suffice to extend the limit. The article presents two arguments in favor of compromise.
In a column for the Hastings Center Report, bioethicist Sarah Chan opens up for discussion whether the 14-day rule could be revised, as it “was not intended to be set in stone” (2017:5). Her arguments put aside concerns about a slippery slope, because moral principles are not being readjusted; the 14-day limit did not establish a “moral bright line” (2017:5) and did not assess when or if embryos acquire moral status.
In this article, bioethicist Sarah Chan examines whether scientific advances in developmental biology should lead to revisiting the 14-day rule. In her view, the Warnock Committee did not arrive at a moral principle or a position on the embryo’s moral status when suggesting the 14-day rule but achieved a policy compromise between concerned parties. However, scientific developments have raised questions as to whether the rule may need to be changed.
In this perspective, the authors, which include a member of the ISSCR, provide a summary of the recommendations of Working Group 2, the sub-committee in charge of updating the 2021 ISSCR guidelines pertaining to oversight processes and the categories of research. They explain the change to the 2016 guidelines, including the categories of review. The new guidelines divide two of the previous three categories. Former category 1, ‘Exempt from review,’ was split in two. Category 2, ‘Requires review,’ remained unchanged.
Known as the Warnock Report, this document primarily deals with issues surrounding in-vitro fertility treatments in the UK. However, it also includes recommendations on related matters of research on human gametes and embryos. One of the many consequential features of the Warnock Report was its advocacy of a fourteen-day limit on the culture of human embryos, the “14-day rule” that eventually made its way into UK law.
In this study led by Ali Brivanlou of Rockefeller University, scientists report the development of an in vitro “attachment platform”: a system that allows the study of the post-implantation development phase of the human embryo. In this arrangement, human blastocysts self-organize to display key events of development that occur in vivo. This novel method builds upon a previous study reported in mice.
This U.S. government report is widely acknowledged to contain (on pages 106-107) the first imposition of a two-week limit on culturing human embryos. It reads "The Ethics Advisory Board finds that it is acceptable from an ethical standpoint to undertake research involving human in vitro fertilization and embryo transfer provided that . . .
The editor of the New Atlantis writes a thought-provoking essay about what he perceives as a lack of limits in biomedical research, expressing concern for research on human-monkey chimeras, and by extension, the 14-day rule of embryo culture. Among the topics that the author takes issue with are the establishment of limits and scientific self-regulation, suggesting that society should not place too much trust on scientists to act responsibly and that strong limits should be put in place.
The author analyzes the evidence and ethical viewpoints that were submitted to the Warnock Committee, and the responses the Warnock Report received after its publication. The committee faced two central questions: 1. When does life begin? 2. Should human embryo research be permitted? The author argues that the Committee adopted a gradualist view of embryonic development.
Spurred by recent announcements that researchers in the UK and USA had sustained human embryos in culture for nearly two weeks, Nature Biotechnology collected commentaries from more than a dozen experts on whether it was time to reassess the 14-day rule. Much of the discussion focuses on the potential benefits of studying the “black box period” of human embryonic development, between about 7 days and 28 days, and on questions of who should decide whether the two-week limit might be breached in the interest of learning more about this period.
The authors suggest that it is time to reassess the 14-day rule, since recent technological advances have made it possible to culture human research embryos for longer periods. A justification for doing so is that the 14-day limit that emerged from US and UK policy in the 1970s and 1980s was decided when culturing embryos close to 14 days was not possible.
In a commentary in Nature, bioethicist Insoo Hyun and research specialists Amy Wilkerson and Josephine Johnston argue that the recent development of capabilities to extend the life of cultured embryos puts research "on a collision course" (2016:170) with the 14-day rule. As a result, the authors argue that the rule and its applications need to be reevaluated. They further claim that the 14-day rule was primarily an instrument of public policy that aimed to enable research while also maintaining public trust.
The International Society for Stem Cell Research (ISSCR) produces research guidelines every five years with the intention of promoting responsible advances in research and clinical applications of stem cell biology. The 2016 guidelines provide a number of recommendations on clinical and ethical principles, including protocols for provision of biomaterials, informed consent processes, documentation, safety and efficacy, privacy, reporting of clinical trials, and other matters for clinical practice.
The ISSCR is an international body founded in 2002 that harmonizes global ethical standards and regulation for research with embryos, stem cells and gametes. The organization updated its 2016 guidelines to accommodate scientific advances in embryo research, embryo models, organoids, chimeras, genome editing, and mitochondrial replacement techniques. Of particular interest is the relaxation of the 14-day rule for in vitro embryo culture. Recommendation 220.127.116.11 of the report puts into question whether certain circumstances justify culture of embryos beyond 14 days.
The authors, renowned bioethicists, responded in June 2021 to the recent May update to the ISSCR guidelines. They argue that the shift in policy from the 2016 guidelines, which maintained the 14-day limit on embryo research, to the updated ISSCR guidelines in 2021 is without sufficient justification. In particular, the authors criticize that the 2021 guidelines do not establish limits for ex vivo embryos. As such, they remind us that limits are necessary for embryo research: “At some point, the developing human embryo reaches a stage at which it should not be used for research.
Robin Lovell-Badge, who chaired the ISSCR’s Task Force to Update the Guidelines, provides an overview of the methods and experts involved in the May 2021 update and defends the rationale for extending the 14-day limit on embryo research to 28 days. According to Lovell-Badge, ISSCR’s guidelines sought to reflect current science without stepping into what research boundaries should be set or were socially acceptable. This is a task would require procedures of public engagement and assessments of public support in recognition of the rule’s status as a compromise in the face of opposition.
This document was written by the 45 members of the International Society for Stem Cell Research (ISSCR) task force charged with revising the Society’s guidelines for stem cell and related biological research. Such revision was necessary, as the task force put it, to “evolve[e] with the science” (2021:1399). They explain their deliberative procedure and highlight the differences between the 2016 and 2021 editions of the guidelines.
A small group of ISSCR affiliates respond to letters from authors who have advocated keeping the 14-day limit. Master and colleagues argue that the 14-day limit “fails to uphold the human right to benefit from science” (2021:494), a right recognized in the 1948 Universal Declaration of Human Rights. This argument seeks to strengthen the main consideration for extending the 14-day limit, allowing science to develop biomedical innovations that would benefit society. It argues that such innovations are inhibited when research is limited.
Published in February 2021 before the ISSCR updated its guidelines, the authors provide an overview of the history of the 14-day rule that originated in the US and the UK, followed by an exposition of the arguments in favor and against extending the rule. They also provide an overview of international legislation and raise questions about oversight mechanisms if the 14-day rule were to be extended internationally. They observe no consensus as to what mix of measures would replace the 14-day rule.
The authors review national policies and legislation for IVF, stem cells and human embryo research in the 22 research and development investing nations, focusing on whether they had restrictions for research on either human embryos or so-called “embryoids.” The review determined whether such research was permitted and whether time limits, such as the 14-day rule, were in place. Their comparison indicates that the adoption of the 14-day rule varies between countries. Of the 22 nations they reviewed, only 14 countries maintain a 14-day limit. Some, such as Switzerland, have a 7-day limit.
The author argues for the extension of the 14-day rule based on potential biomedical and therapeutic applications and the lack of “coherent or persuasive reasons to deny researchers, and through them humanity, the knowledge and the innovation that this will generate” (2021:e66). In particular, the author argues that the use of animal models cannot fill the gaps left by the absence of human embryo research, as there are research questions that can only be addressed with their examination.
The authors, President and Director of Policy at ISSCR, provide an overview of the updates and rationale for the changes suggested in the 2021 ISSCR guidelines. The guidelines propose three categories of oversight for stem-cell and embryo research, with new distinctions between restricted research and research considered unethical until further safety considerations are determined. The authors note that the scope of the guidelines includes human embryos and embryo models, organoids, chimeric embryos, mitochondrial replacement techniques, and heritable genome editing.
The UK’s independent Nuffield Council of Bioethics convened an expert workshop to respond to the question of whether the 14-day rule should be reevaluated in the wake of new technological developments. The Council explains the logic underlying the initial establishment of the rule and the UK’s specific legal mechanisms providing licensed exceptions for research on embryos younger than two weeks.
Renowned theologian Ted Peters defends the 14-day rule because it places human dignity and reverence for human life at the heart of the debate, providing a counterweight to the materialism and utilitarianism pervasive in scientific research. Furthermore, the author does not find justifiable ISSCR’s arguments for extending the 14-day limit, which reflects a lack of scientists’ engagement with religious arguments that prioritize human dignity and its sacredness. This suggests that scientists consider moral concerns about scientific research unnecessary and inhibitory of scientific advancement.
Stem cell biologist Jane Rossant provides an excellent explanation of efforts and publications by Shahbazi et al. (2016) and Deglincerti et al. (2016) to culture self-organizing human embryos in vitro. Rossant attributes their achievements mainly to “an improved culture medium and a better substrate for embryo attachment” (2016:182). Prior to the new developments, the period beyond one week of human embryonic development had been a blackbox, since at this point the embryo would have to be implanted.
Japanese bioethicists and scholars defend the 14-day rule, pointing out that it was a promise and compromise that helped secure public trust in biomedicine. They also draw attention to concerns raised by others in the wake of the ISSCR’s 2021 revised guidelines. First, the ISSCR made its decision without sufficient public debate. Second, the ISSCR did not set a new limit for embryo culture in vitro. Overall, the authors “get the impression that the ISSCR’s justification does not give enough consideration to moral concerns vis-à-vis scientific merits” (2021:e53726).
This study led by Magdalena Zernicka-Goetz at the University of Cambridge reports the development of an “in vitro system to culture human embryos through implantation stages” (2016:700) in the absence of maternal tissues, which were previously thought to be required to mimic the implantation of an embryo in an uterus. The scientists adapted a protocol for mouse embryo culture, using an extracellular matrix. Implantation is a milestone in human development, thought to induce remodeling of the embryo and gastrulation.
Writing in Nature, science writer Elizabeth Svoboda describes the recent technological developments that have potential to provide new knowledge about the early stages of human development and lead to the production of a new range of therapeutic interventions. These developments test the limits of embryo research by extending its feasibility and producing a new range of “near-human embryonic structures” (2021:S16) that become objects of uncertain standing.
LeRoy Walters, Georgetown bioethicist and one of the authors of the report of the Ethics Advisory Board report on in vitro fertilization (IVF), reflects on the trajectory that federal policy on human embryo followed in the decades after the report’s publication. Walters argues that different presidential administrations in the United States have ignored the ethics of embryo research and have generally lacked decisive action, for which the United Kingdom set a model example.
In a lecture given at Ormond College, Melbourne in July 1986, Mary Warnock provides a summary of the questions and moral dilemmas faced by the committee that she presided over, the Committee of Inquiry into Human Fertilization and Embryology. Warnock provides an overview of the moral reasoning behind the protection or use of human embryos in research, followed by an overview of how some of these arguments played out in the committee. These include the establishment of the appearance of a primitive streak and the 14-day rule as a cutoff for embryo policy.
The author examines Mary Warnock’s role leading her namesake committee in the UK during the 1980s to show how bioethics gained traction and became institutionalized in Britain. British bioethics responded to concerns that were different from those in the US, particularly the need to exert external oversight and scrutiny of scientific activities. Wilson’s account suggests that this oversight was necessary for research to continue.
In Experiments in Democracy, Observatory Co-Director Ben Hurlbut traces a history of the American debates, forms of reasoning, norms, and institutional struggles that have faced the moral status of the human embryo and justified its use for research purposes. In the first chapter, he examines the ethics and politics of reproductive rights and research in the US, from the mid-1960s to 1980.
In this seminal book, Observatory Director Sheila Jasanoff explains the reasons behind the different paths that the US, the UK, and Germany have taken in biotechnology policy and regulation. This includes different political cultures and ways of public reasoning and decision-making, which she captures with the concept of “civic epistemology.” Chapter 6 focuses on debates and moral dilemmas that surrounded the emergence of IVF and the “technological capacity to manipulate human life” (2005:146).
Observatory Director Sheila Jasanoff identifies that the processes of making sense of ambiguous biological entities—like human embryos—are also political processes that settle questions of ethical responsibility toward these entities. These processes draw on established national scripts for ordering the relationship between science and politics. She characterizes the formulation of the 14-day rule as an act of “ontological surgery” that drew a line at two weeks between the nonhuman and human as research subject.
In chapter 4 of the book Making Sense of Life, Observatory Director Sheila Jasanoff reflects on the challenges that new entities created through biotechnology as ‘moral grey zones’ bring to democratic societies as filled with moral questions. Such biological objects include the cloning of Dolly the Sheep, “three-parent embryos,” human embryonic stem cells (hESCs), and spare embryos created for IVF purposes.
This book provides an account of the events and public debate that took place between the commissioning of the Warnock Committee in 1982, to the 1990 passage of legislation that approved embryo research under certain conditions. In the 1980s, Britain experienced lively debates about whether human embryo research should be permitted and even considered a complete ban. The book traces the efforts of groups with different ideological and moral commitments to determine the future of embryo research in the UK, from initial mistrust and disapproval to permissibility.
This chapter refers to the biology behind embryonic stem cell (ESC) research and the question of permissibility of using human embryos in such research. Steinbock concludes that the creation and destruction of human embryos is justified as the aim is to improve people’s lives, which is not equivalent to disrespecting human life. The chapter provides an overview of different criteria that assign moral status to human embryos, such as their biological humanity, which considers embryos as having moral status and moral rights by virtue of being members of the Homo sapiens species.