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CRISPR's Twisted Tales: Clarifying Misconceptions about Heritable Genome Editing
Abstract
The raging controversy about whether heritable genome editing should be permitted is shaped and structured by the prevailing and countervailing narratives in circulation. In recent years, considerable shortcomings have come to characterize this discourse; it is now time to identify and correct a number of serious misunderstandings and distortions that have taken hold. This essay begins by briefly evaluating reactions to the November 2018 announcement that gene-edited babies had been born; it asserts that widespread agreement about the researcher's recklessness and dire ethical violations concealed deep fault lines among participants in the heritable genome editing debate. It goes on to consider several key omissions and misrepresentations that distort public understanding and undermine genuine debate. It suggests that the conversation must be refocused away from technical, medical, and scientific considerations toward matters of societal meanings, values, context, and consequences. It concludes with criteria for a broadly inclusive and meaningful decision-making process about whether heritable genome editing has any place in the shared and just future to which we aspire.
... Since the myopia of biomedicine does not often yield elegantly to balance of risk considerations, these issues must, ultimately, be decided by sectors of society not involved in direct or indirect financial gain from adoption. Darnovsky and Hasson (2020) correctly call for cultural input from sectors of our societies far removed from science; Chan (2020) has called for global regulation, but by means unknown. I would add that those who stand to financially benefit be excluded from debates on the moral questions around adopting biotransformative technologies. ...
Human evolution sits at several important thresholds. In organic evolution, interplay between exogenous environmental and genetic factors rendered new phenotypes at rates limited by genetic variation. The interplay took place on adaptive fitness landscapes determined by correspondence of genetic and environmental relationships. Human evolution involved important emergences that altered the adaptive landscape: language, writing, organized societies, science, and the internet. These endogenous factors ushered in transformative periods leading to more rapidly evolving emergences. I explore the impact of development of emerging biotransformative technologies capable of being applied to effect self-genetic modification and artificial intelligence-augmented cognition on the evolutionary landscape of phenotypes important to cognitive plasticity. Interaction effects will yield unanticipated emergences resulting in hyperrealm adaptive landscapes with more rapid evolutionary processes that feed back upon more fundamental levels while vastly outpacing organic evolution. Emerging technologies exist that are likely to impact the evolution of cognitive plasticity in humans in ways and at rates that will lead to societal upheaval. I show that the theoretical contribution of organic evolution in future human evolution is expected to become comparatively insignificant relative to that made by endogenous environmental factors such as external cognition aids and manipulation of the human genome. The results support the conclusion of a strong recommendation of a moratorium on the adoption of any technology capable of completely altering the course of human evolution.
This study investigated youths’ empowerment through EU-funded climate change projects (CCPs) and the role that social research and public engagement have in that process. The importance of considering youth empowerment in a time of climate change is increasingly recognised. Youths are exposed to interrelated health, social, economic, and political vulnerabilities caused by climate change, but they often have limited resources to address and navigate these changes. To help address these issues youth empowerment holds the potential to give youth a greater influence over their life in the context of evolving climate change. EU-funded CCPs plays a crucial role in EU’s climate mitigation and adaption policies and the implementation of these projects can have widespread implications for youth across the EU. However, despite this, there is little research that explores the local youth implications of EU-funded CCPs. In this paper we want to start addressing this knowledge gap by exploring how youth empowerment was facilitated, shaped, and restrained over a year-long collaboration with students from a Greek school as part of an EU Horizon 2020 project on social acceptance of Carbon Capture and Utilisation (CCUS) technologies. The findings indicate that the activities provided the students with opportunities to explore and express different types of concerns, knowledges and perspectives on issues related to climate change, social acceptance and CCUS. However, the empowering potential of these activities were also shaped by power differentials and contestations around what types of knowledge should matter and the source of that knowledge. Although the capacity to engage with youth through Horizon 2020 resources is feasible, more longitudinal and meaningful participation is needed.
Human germline editing refers to the process of making changes to the genetic material of human embryos, eggs, or sperm cells, which can then be passed on to future generations. It is a highly controversial and ethically complex field of research. The ability to precisely and easily alter the DNA sequences of living things has been made possible by new biochemical techniques. The potential of these new tools to deepen our understanding of biology, change the genomes of microorganisms, plants, and animals, and treat human diseases has caused enormous enthusiasm in the scientific and medical communities. They have also sparked important discussions about how people might decide to change future generations' genomes as well as their own. This chapter focus on the human germline editing with reconciling scientific progress with rogues and legal framework global observatory and its inherent conundrums.
The concept of vulnerability has become widely acknowledged as a fundamental concept for medical ethics and research ethics, yet rarely considered with respect to ethical assessments of human germline genome editing. A first aim of this paper is to make vulnerability ethics considerations fruitful for issues related to these technical innovations. The possibility of altering the genome promises to overcome forms of vulnerability inherently connected to our existence as physical beings and would hence allow to increase the resilience of human nature or even to move evolution forward by equipping people with new character traits and enhanced capabilities. I suggest a more fine-grained distinction of various applications purposes than the dichotomy of therapeutic and enhancement. I support the rejection of most application purposes as ‘therapeutic’ and claim that framing them as ‘therapeutic’ in the context of the current discursive constellation runs the risk of accentuating existing vulnerabilities. With respect to intergenerational responsibilities, I reject the view that editing the germline necessarily leads to corrupt intergenerational relations based on which it must be categorically excluded. I conclude that it is nevertheless important to take a very close look at the challenges that arise, especially from a vulnerability perspective, before irreversible facts are created overhastily.
Ever since the publication of Derek Parfit’s Reasons and Persons, bioethicists have tended to distinguish between two different ways in which reproductive technologies may have implications for the welfare of future persons. Some interventions harm or benefit particular individuals: they are “person affecting.” Other interventions determine which individual, of a number of possible individuals, comes into existence: they are “identity affecting” and raise the famous “non-identity problem.” For the past several decades, bioethical debate has, for the most part, proceeded on the assumption that direct genetic modification of human embryos would be person affecting. In this paper, I argue that that genome editing is highly unlikely to be person affecting for the foreseeable future and, as a result, will neither benefit nor harm edited individuals.
As public interest advocates, policy experts, bioethicists, and scientists, we call for a course correction in public discussions about heritable human genome editing. Clarifying misrepresentations, centering societal consequences and concerns, and fostering public empowerment will support robust, global public engagement and meaningful deliberation about altering the genes of future generations.
CRISPR is widely considered to be a disruptive technology. However, when it comes to the most controversial topic, germline genome editing (GGE), there is no consensus on whether this technology has any substantial advantages over existing procedures such as embryo selection after in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD). Answering this question, however, is crucial for evaluating whether the pursuit of further research and development on GGE is justified. This paper explores the question from both a clinical and a moral viewpoint, namely whether GGE has any advantages over existing technologies of selective reproduction and whether GGE could complement or even replace them. In a first step, I review an argument of extended applicability. The paper confirms that there are some scenarios in which only germline intervention allows couples to have (biologically related) healthy offspring, because selection will not avoid disease. In a second step, I examine possible moral arguments in favour of genetic modification, namely that GGE could save some embryos and that GGE would provide certain benefits for a future person that PGD does not. Both arguments for GGE have limitations. With regard to the extended applicability of GGE, however, a weak case in favour of GGE should still be made.
We review the Nuffield Council on Bioethics 2018 report on germline gene editing and show how its shortcomings are part of an increasingly permissive climate among elite scientists that may well have emboldened the Chinese 'CRISPR babies' experiment. Without a robust and meaningful airing of the perils of human germline modification, these views are likely to encourage additional, more mainstream moves in the same dangerous direction.
https://rcdu.be/brcsl.
Millions of people now access personal genetic risk estimates for diseases such as Alzheimer’s, cancer and obesity¹. While this information can be informative2–4, research on placebo and nocebo effects5–8 suggests that learning of one’s genetic risk may evoke physiological changes consistent with the expected risk profile. Here we tested whether merely learning of one’s genetic risk for disease alters one’s actual risk by making people more likely to exhibit the expected changes in gene-related physiology, behaviour and subjective experience. Individuals were genotyped for actual genetic risk and then randomly assigned to receive either a ‘high-risk’ or ‘protected’ genetic test result for obesity via cardiorespiratory exercise capacity (experiment 1, N = 116) or physiological satiety (experiment 2, N = 107) before engaging in a task in which genetic risk was salient. Merely receiving genetic risk information changed individuals’ cardiorespiratory physiology, perceived exertion and running endurance during exercise, and changed satiety physiology and perceived fullness after food consumption in a self-fulfilling manner. Effects of perceived genetic risk on outcomes were sometimes greater than the effects associated with actual genetic risk. If simply conveying genetic risk information can alter actual risk, clinicians and ethicists should wrestle with appropriate thresholds for when revealing genetic risk is warranted. © 2018, The Author(s), under exclusive licence to Springer Nature Limited.
Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.
Genome editing has potential for the targeted correction of germline mutations. Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR-Cas9-based targeting accuracy and high homology-directed repair efficiency by activating an endogenous, germline-specific DNA repair response. Induced double-strand breaks (DSBs) at the mutant paternal allele were predominantly repaired using the homologous wild-type maternal gene instead of a synthetic DNA template. By modulating the cell cycle stage at which the DSB was induced, we were able to avoid mosaicism in cleaving embryos and achieve a high yield of homozygous embryos carrying the wild-type MYBPC3 gene without evidence of off-target mutations. The efficiency, accuracy and safety of the approach presented suggest that it has potential to be used for the correction of heritable mutations in human embryos by complementing preimplantation genetic diagnosis. However, much remains to be considered before clinical applications, including the reproducibility of the technique with other heterozygous mutations.
Heritable human genetic modifications pose serious risks, and the therapeutic benefits are tenuous, warn Edward Lanphier, Fyodor Urnov and colleagues.
STS research has devoted relatively little attention to the promotion and reception of science and technology by non-scientific actors and institutions. One consequence is that the relationship of science and technology to political power has tended to remain undertheorized. This article aims to fill that gap by introducing the concept of “sociotechnical imaginaries.” Through a comparative examination of the development and regulation of nuclear power in the US and South Korea, the article demonstrates the analytic potential of the imaginaries concept. Although nuclear power and nationhood have long been imagined together in both countries, the nature of those imaginations has remained strikingly different. In the US, the state’s central move was to present itself as a responsible regulator of a potentially runaway technology that demands effective “containment.” In South Korea, the dominant imaginary was of “atoms for development” which the state not only imported but incorporated into its scientific, technological and political practices. In turn, these disparate imaginaries have underwritten very different responses to a variety of nuclear shocks and challenges, such as Three Mile Island (TMI), Chernobyl, and the spread of the anti-nuclear movement.
How new biomedical technologies—from prenatal testing to gene-editing techniques—require us to imagine who counts as human and what it means to belong.
From next-generation prenatal tests, to virtual children, to the genome-editing tool CRISPR-Cas9, new biotechnologies grant us unprecedented power to predict and shape future people. That power implies a question about belonging: which people, which variations, will we welcome? How will we square new biotech advances with the real but fragile gains for people with disabilities—especially when their voices are all but absent from the conversation?
This book explores that conversation, the troubled territory where biotechnology and disability meet. In it, George Estreich—an award-winning poet and memoirist, and the father of a young woman with Down syndrome—delves into popular representations of cutting-edge biotech: websites advertising next-generation prenatal tests, feature articles on “three-parent IVF,” a scientist's memoir of constructing a semisynthetic cell, and more. As Estreich shows, each new application of biotechnology is accompanied by a persuasive story, one that minimizes downsides and promises enormous benefits. In this story, people with disabilities are both invisible and essential: a key promise of new technologies is that disability will be repaired or prevented.
In chapters that blend personal narrative and scholarship, Estreich restores disability to our narratives of technology. He also considers broader themes: the place of people with disabilities in a world built for the able; the echoes of eugenic history in the genomic present; and the equation of intellect and human value. Examining the stories we tell ourselves, the fables already creating our futures, Estreich argues that, given biotech that can select and shape who we are, we need to imagine, as broadly as possible, what it means to belong.
Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic; the majority of inherited susceptibility is related to the cumulative effect of many common DNA variants. Here we derive and validate a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and test this predictor in more than 300,000 individuals ranging from middle age to birth. Among middle-aged adults, we observe a 13-kg gradient in weight and a 25-fold gradient in risk of severe obesity across polygenic score deciles. In a longitudinal birth cohort, we note minimal differences in birthweight across score deciles, but a significant gradient emerged in early childhood and reached 12 kg by 18 years of age. This new approach to quantify inherited susceptibility to obesity affords new opportunities for clinical prevention and mechanistic assessment.
Eric Lander, Françoise Baylis, Feng Zhang, Emmanuelle Charpentier, Paul Berg and specialists from seven countries call for an international governance framework. Eric Lander, Françoise Baylis, Feng Zhang, Emmanuelle Charpentier, Paul Berg and specialists from seven countries call for an international governance framework. Embryo culture dish used for in vitro fertilisation
Audio Interview
Interview with Dr. George Daley on the prospects for using genome editing to prevent genetic diseases. (10:11)Download
Calling for a moratorium on germline editing won’t stop rogue actors. Instead, an “ecosystem” approach to regulation might minimize premature, unwarranted, or dangerous research and complement efforts to develop a consensus about acceptable and unacceptable uses.
The scientific community’s response to the CRISPR twins should not pre-empt broader discussion across society, warns J. Benjamin Hurlbut. The scientific community’s response to the CRISPR twins should not pre-empt broader discussion across society, warns J. Benjamin Hurlbut.
The Second International Summit on Human Genome Editing, held in Hong Kong last month, was rocked by the revelation from a researcher from Shenzhen that twins were born whose healthy embryonic genomes had been edited to confer resistance to HIV. Despite widespread condemnation by the summit organizing committee, world scientific academies, and prominent scientific leaders that such research was “deeply disturbing” and “irresponsible,” and the launch of an investigation in China into the researcher's actions, it is apparent that the ability to use CRISPR-Cas9 to edit the human genome has outpaced nascent efforts by the scientific and medical communities to confront the complex ethical and governance issues that they raise. The current guidelines and principles on human germline genome editing are based on sound scientific and ethical principles. However, this case highlights the urgent need to accelerate efforts to reach international agreement upon more specific criteria and standards that have to be met before human germline editing would be deemed permissible.
A new infrastructure is urgently needed at the global level to facilitate exchange on key issues concerning genome editing. We advocate the establishment of a global observatory to serve as a center for international, interdisciplinary, and cosmopolitan reflection. This article is the first of a two-part series.
Sheila Jasanoff and J. Benjamin Hurlbut call for an international network of scholars and organizations to support a new kind of conversation.
‘Mitochondrial replacement’ and ‘germline gene editing’ are relatively new techniques that represent a significant moral, technological, and legal threshold, as they would introduce permanent and heritable changes to the human gene pool. This article examines the close relationship between these two technologies over time, considering what regulatory lessons can be learned from the former as attention turns to the latter. It argues that the UK’s ‘mitochondrial replacement’ approval process should not be taken as a model for the wider regulation of germline gene editing, and that policy-making needs to contend with a comprehensive picture of the social and political meaning of these technologies in the world.
Genome editing is a powerful new tool for making precise alterations to an organism’s genetic material. Recent scientific advances have made genome editing more efficient, precise, and flexible than ever before. These advances have spurred an explosion of interest from around the globe in the possible ways in which genome editing can improve human health. The speed at which these technologies are being developed and applied has led many policymakers and stakeholders to express concern about whether appropriate systems are in place to govern these technologies and how and when the public should be engaged in these decisions. © 2017 by the National Academy of Sciences. All rights reserved.
A framework for open discourse on the use of CRISPR-Cas9 technology to manipulate the human genome is urgently needed.
Copyright © 2015, American Association for the Advancement of Science.
Exploring in depth one of the most topical subjects of current affairs, this book explains the science of embryology, exploring what science can and will be able to do to affect the natural processes, through a series of individual stories, both contemporary and imagined.
Before Heritable Genome Editing, We Need Slow Science and Dialogue 'Within and Across Nations
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Scientists Disagree About the Ethics and Governance of Human Germline Editing
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Dare We Edit the Human Race? Star Geneticists Wrestle with their Power
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As Calls Mount to Ban Embryo Editing with CRISPR, Families Hit by Inherited Diseases Say, Not So Fast
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Gene-Edited Babies: What a Chinese Scientist Told an American Mentor
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Broad Public Support for '3-Parent Babies' and Crossing the Human Germline? Not What the Data Say
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The Most Worrying Thing About Gene Editing Is That It's Really Easy
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Editorial Precision? Snapshot of CRISPR Germline in the News
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Are Scientists' Reactions to 'CRISPR Babies' About Ethics or Self-Governance?
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Gene-Edited Chinese Babies May Have 'Enhanced Brains' Scientists Say
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Why Making A 'Designer Baby' Would Be Easier Said Than Done
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Gene-Edited Babies: No One Has the Moral Warrant to Go It Alone
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Genetically-Modified Babies to Become 'SUPERHUMANS with Enhanced Brains', Scientist Warns
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The Chinese Gene-Editing Experiment Was an Outrage: The Scientific Community Shares Blame
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Fertility Clinics Industry in the US: Market Research Report
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Those Designer Babies Everyone Is Freaking Out About-It's Not Likely to Happen
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Can Science Make Sense of Life
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A Conversation with George Church on Genomics and Germline Human Genetic Modification
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Group Pulls Video That Stirred Talk of Designer Babies
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Climate Change Is 'Greatest Challenge Humans Have Ever Faced
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