Heritable Genome Editing: Is a Moratorium Needed?

Writing in the Journal of the American Medical Association, biomedical scientist Eli Adashi and legal scholar Glenn Cohen detail some of the arguments against moratoria from the perspective of leading genome editing scientists. They criticize moratoria for several reasons: slowing scientific progress, withholding potential medical treatments, increasing medical tourism, favoring ideology over pure scientific inquiry, being overly broad and thus producing unintended effects, and simply being unnecessary given the capacity of scientists to self-regulate.

New guidelines for stem cell and embryo research from the ISSCR

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.

Should the 14-day rule for embryo research become the 28-day rule?

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.

Call for moratorium on xenotransplants

Two Harvard University researchers call for a moratorium on clinical trials of xenotransplantation in a brief Nature commentary. They specifically invoke the precedent of Asilomar as a “turning point” for scientists’ approach to public responsibility. They suggest that the decisions of whether and how to proceed with such clinical trials should not be left to technical experts alone, instead requiring “an informed public debate.” They identify a single chief risk of xenotransplantation research: the potential of a pathogen to cross the species barrier.

A prudent path forward for genomic engineering and germline gene modification

A collection of prominent scientific researchers call for open discourse on the potential applications of CRISPR/Cas9 to modify the human genome. These researchers, among whom are several organizers of the Asilomar Conference on Recombinant DNA, also gathered in California—a bit north of Asilomar, in Napa—to discuss the prospects of an emerging technology of concern. Following this meeting, the authors make several recommendations.

The recombinant DNA controversy: twenty years later.

Paul Berg, one of the scientists behind the original call for a voluntary moratorium on recombinant DNA research, and Maxine Singer, another molecular biologist and fellow Asilomar organizer, reflect on the legacy of Asilomar 20 years after the conference. They identify Asilomar “the beginning of an exceptional era for science and for the public discussion of science policy—one that continues unabated to this day.” They note the universal observance of the voluntary moratorium as evidence of its success.

Potential Biohazards of Recombinant DNA Molecules

A committee of prominent genetic researchers writing on behalf of the Assembly of Life Sciences and the National Research Council (NRC) call for action to address concerns around recombinant DNA. This action includes “voluntarily deferring” several types of scientific experimentation, generally involving the dissemination of potentially harmful plasmids. They also include the formation of an advisory committee to oversee experiments and develop guidelines and procedures for potentially hazardous research.

Why we should not extend the 14-day rule

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.

How to Rethink the Fourteen-Day Rule

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.

Human embryo research, stem cell-derived embryo models and in vitro gametogenesis: Considerations leading to the revised ISSCR guidelines

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.

CRISPR's unwanted anniversary

In this brief opinion piece, one of CRISPR/Cas9’s lead developers, Jennifer Doudna, marks the one-year anniversary of the reveal of He Jiankui’s experiments. Doudna identifies the response form the global scientific community as “encouraging,” believing that it created the possibility for broade4r conversations about CRISPR’s applications. However, she also orients this conversation toward transparency and responsible application of CRISPR and foregrounds health and safety concerns.

Just Say No to Human-Monkey Chimeras

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.

Human genome editing: ask whether, not how

Observatory Co-Director Ben Hurlbut argues in Nature that reaction in the wake of the reveal of He Jiankui’s CRISPR/Cas9 experiments risks presuming the inevitability of human germline genome editing. It thereby prematurely forecloses broader debate about whether germline editing should happen at all. Hurlbut highlights the Global Observatory’s efforts as one “modest experiment” to challenge this foreclosure and, following Hannah Arendt, help us build the capacities to think and speak more clearly that which we do.

Revisiting the Warnock rule

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.

Embryology policy: Revisit the 14-day rule

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.

Democratic Governance of Human Germline Genome Editing

An international regulatory commission convened by scientific academies is a premature and problematic approach to governing human germline genome editing. Given the complex, international landscape of genome editing and significant cross-national differences among regulatory cultures, deferring to a single commission to set the agenda for global governance raises troublesome questions of framing and representation.

ISSCR: grave omission of age limit for embryo research

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.

Adopt a moratorium on heritable genome editing

Following the reveal of He Jiankui’s experiments, Eric S. Lander and colleagues—a collection of scientists and bioethicists across seven countries—argue in favor of a global moratorium on heritable human genome editing. The moratorium that they call for beings as absolute, but following the development of an international framework, permissions to engage in human germline editing would be decided on a nation-by-nation basis. They suggest the World Health Organization (WHO) as a potential institution to oversee the construction of a global framework via an international panel.

Stem-cell guidelines: why it was time for an update

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.

ISSCR guidelines uphold human right to science for benefit of all

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.

Rethinking Human Embryo Research Policies

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 time has come to extend the 14-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.

New guidelines for embryo and stem cell research

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.

Keep the 14-Day Rule in Stem Cell Research

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.

Promises and rules

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).

A case against a moratorium on germline gene editing

Reflecting on Lander et al.’s call for a moratorium on human germline gene editing, biomedical ethicist G. Owen Schaefer makes several arguments why a moratorium is neither desirable nor necessary while also emphasizing the importance of greater public deliberation. Interestingly, he includes whether to impose a moratorium on human germline gene editing research as a decision that should require public input.

A Voluntary Moratorium?

In this brief piece, then-Editor-in-Chief of Molecular Therapy draws on the occurrence of multiple adverse events in clinical trials of retrovirus-mediated gene therapies to address the question of whether a voluntary moratorium is necessary. Verma argues that it is not, on the grounds that it is difficult to identify the root causes of the adverse events and that a moratorium would be unfair to potential gene therapy patients.

Human Embryo Research: Lessons from History

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.