Recent reports of CRISPR/Cas9 genome editing in parasitic helminths open up new avenues for research on these dangerous pathogens. However, the complex morphology and life cycles inherent to these parasites present obstacles for the efficient application of CRISPR/Cas9‐targeted mutagenesis. This is especially true with the trematode flukes where only modest levels of gene mutation efficiency have been achieved. Current major challenges in the application of CRISPR/Cas9 for study of parasitic worms thus lie in enhancing gene mutation efficiency and overcoming issues (...) involved in host passage so that mutated parasites survive. Strategies developed for CRISPR/Cas9 studies on Caenorhabditis elegans, protozoa and mammalian cells, including novel delivery methods, the choice of selectable markers, and refining mutation precision represent novel tactics whereby these impediments can be overcome. Furthermore, employing CRISPR/Cas9‐mediated gene drive to interfere with vector transmission represents a novel approach for the control of parasitic worms that is worthy of further exploration. (shrink)

Although germline editing has been the subject of debate ever since the 1980s, it tended to be based rather on speculative assumptions until April 2015, when CRISPR/Cas9 technology was used to modify human embryos for the first time. This article combines knowledge about the technical and scientific state of the art, economic considerations, the legal framework and aspects of clinical reality. A scenario will be elaborated as a means of identifying key ethical implications of CRISPR/Cas9 genome editing in humans and (...) possible ways of dealing with them. Unlike most other discussions of CRISPR/Cas9 germline editing, which are generally based on deontological arguments, the focus in this case will be on a consequentialistic argument against certain applications of germline and somatic editing that takes not only the potential benefits and risks but also socioeconomic issues into consideration. The practical need for an indication catalogue, guidelines for clinical trials, and for funding of basic research will be pointed out. It will be argued that this need for regulatory action and discussion does not stem primarily from the fact that CRISPR/Cas9 germline editing is revolutionary in terms of its ethical implications and potential for human therapy, although this is the prevailing view in the current discussion. Understanding the value and interest dependency of arguments put forward by different stakeholders and learning from past debates related to similar technologies might prove a fruitful method of reaching judgments and decisions that come closer to a consensus upon which society as a whole can agree - which after all should be the true goal of an ethical debate and of bioethics. (shrink)

The discovery of clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-mediated protein 9 (CRISPR-Cas9) immediately revealed numerous potential therapeutic applications. Although CRISPR-Cas9 will most likely be useful for addressing issues such as genetic diseases and related medical issues, use of this modality for germline modification generates complex ethical questions regarding the safety and efficacy, human genetic enhancement, and “designer” babies. In this article, the case of the He Jiankui affair is used as an example of the potential for (...) unregulated use of CRISPR-Cas9 technology. In 2018, Dr He Jiankui reported that he had successfully edited human embryos. This work clearly violates all international principles of bioethics. As such, the purpose of this paper is to explore the ethical challenges inherent in the use of CRISPR-Cas9 for human germline editing from the perspectives of the goals of Islamic law (Maqasid al Shari'a) and the major jurisprudential maxims (Qawaid Fiqhiyyah). We argue that from an Islamic standpoint, the therapeutic application of CRISPR-Cas9 for germline editing may be permissible if the safety and efficacy concerns are resolved and if the principles of Maqasid al-Shari'a are fulfilled. (shrink)

Recently, Chinese researchers published the results of their research using a gene-editing technology on abnormal human zygotes. The research team believes this research has prospective clinical application, viz., for gene therapy for?-thalassemia, a white blood cell disorder, and plan to persist with further studies, despite technical problems in this experiment. The research has elicited international criticism from both scientific and bioethics domains, because it innovates beyond the current global consensus against human germ line modification. This paper comments on some ethical (...) issues presented by the research report and concludes that, under present circumstances, the Chinese research team did not meet a standard of scientific responsibility.Bangladesh Journal of Bioethics 2015 Vol.6 (1):22-26. (shrink)

The CRISPR-Cas9 system is a genetic editing technology that, in addition to expanding the possibilities for scientific research, promotes reflections associated with human dignity, biological control, therapy, and genetic improvement. Bioethical discussions on the challenges and repercussions of the CRISPR-Cas9 system are reviewed. As a result, bioethical questions tend to problematize the application to non-human organisms, primary research, and the human somatic and germline. In brief, it is necessary to increase the levels of safety and effectiveness so that the benefits (...) outweigh the risks, while reducing bioethical concerns and increasing the credibility of the technique. (shrink)

The recent development of CRISPR/Cas9 technology has rekindled the ethical debate concerning human germline modification that has begun decades ago. This inexpensive technology shows tremendous promise in disease prevention strategies, while raising complex ethical concerns about safety and efficacy of the technology, human dignity, tampering with God’s creation, and human genetic enhancement. Germline gene editing may result in heritable changes in the human genome, therefore the question of whether it should be allowed requires deep and careful discussion from various perspectives. (...) This paper explores Islamic perspectives on the concerns raised and highlights the ethical principles in Islam that should be taken into consideration when assessing the permissibility of CRISPR/ Cas9-mediated human germline gene editing. As argued in this paper, human germline gene editing would be considered lawful for medical purpose under certain conditions. It should not be applied on humans until the safety and efficacy issues are resolved. Robust ethical guidelines and strict regulations are necessary to preserve human dignity and to prevent premature and misuse of the technology. Maqasid al-shariah’s principles of preservation of human life, lineage, and dignity and ‘preventing harm takes precedence over securing benefit’ are among the guiding principles in assessing the permissibility of CRISPR/Cas9-mediated human germline editing from an Islamic perspective. Further discussions are important to address the controversies as well as to explore the related ethical principles. (shrink)

In 2015 scientists called for a partial ban on genome editing in human germline cells. This call was a response to the rapid development of the CRISPR–Cas9 system, a molecular tool that allows researchers to modify genomic DNA in living organisms with high precision and ease of use. Importantly, the ban was meant to be a trust-building exercise that promises a ‘prudent’ way forward. The goal of this paper is to analyse whether the ban can deliver on this promise. To (...) do so the focus will be put on the precedent on which the current ban is modelled, namely the Asilomar ban on recombinant DNA technology. The analysis of this case will show (a) that the Asilomar ban was successful because of a specific two-step containment strategy it employed and (b) that this two-step approach is also key to making the current ban work. It will be argued, however, that the Asilomar strategy cannot be transferred to human genome editing and that the current ban therefore fails to deliver on its promise. The paper will close with a reflection on the reasons for this failure and on what can be learned from it about the regulation of novel molecular tools. (shrink)

In 2016, a new technique to edit genes was made public: the CRISPR-CAS9. Five years later, we can examine the advancement of this biotechnology from bioethics. It is evident that the gene-editing technique on the somatic line has been disseminated and is starting to show some results. Nonetheless, it is impossible to extend this work to the germlines through heritable human genome editing. Two documents are studied, the International Commission for the Clinical Use of Human Germline Genome Editing report and (...) the World Health Organization Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing report, reflecting on their content and consequences. (shrink)

CRISPR/Cas9 is quickly becoming one of the most influential biotechnologies of the last five years. Clinical trials will soon be underway to test whether CRISPR/Cas9 can edit away the genetic mutations that cause sickle cell disease (SCD). This article will present the background of CRISPR/Cas9 gene editing and SCD, highlighting research that supports the application of CRISPR/Cas9 to SCD. While much has been written on why SCD is a good biological candidate for CRISPR/Cas9, less has been written on the ethical (...) implications of including SCD in CRISPR/Cas9 research. This article will argue that there is a strong case in favor of including SCD. Three benefits are achieving distributive justice in research, continuing to repair the negative relationship between patients with SCD and the health‐care system, and benefit‐sharing for those who do not directly participate in CRISPR/Cas9 research. Opponents will argue that SCD is a risky candidate, that researchers will not find willing participants, and that the burden of SCD is low. Of this set of arguments, the first gives pause. However, on balance, the case in favor of including SCD in CRISPR/Cas9 research is stronger than the case against. Ultimately, this article will show that the historic and sociopolitical injustices that impede progress in treating and curing SCD can be alleviated through biotechnology. (shrink)

Biomedical research, on the one hand, contributes to important goals from generation of knowledge about the human body to the development and testing of therapeutics of all kinds. On the other hand, it can produce serious and sometimes unforeseeable consequences. In the ethical analysis of these two aspects of biomedical research, two important argumentative strategies play a major role. First, slippery slope arguments are used to warn of potential risks and to highlight knowledge-based limitations. Second, a dual-use problem describes the (...) challenge that already established techniques can be used for both morally wrong and morally right purposes. These two argumentative strategies appear to share several similarities, which will be investigated in this article. For this purpose, the article will first provide clear working definitions for both types of argument. This lays the foundation for the further ethical analysis. In a second step, and in order to investigate the similarities and differences of the argumentative strategies with an example from current ethical debates, CRISPR-Cas9, a currently very promising tool of genome editing, will be examined. The extent to which the possible applications of this genome editing tool can be addressed by slippery slope arguments or the dual use problem will be investigated. For this purpose, selected studies involving the use of CRISPR-Cas9 will be examined. Based on this two-step, analytic and example-based comparison of slippery-slope argumentation and dual-use considerations, the article will detail the ethically relevant difference between the two argumentative strategies and at the same time contribute to the ongoing ethical debate about CRISPR-Cas9. (shrink)

In 2015 a team of scientists used a new gene-editing technique called CRISPR-Cas9 to edit the genome of 86 non-viable human embryos. The experiment sparked a global debate on the ethics of gene editing. In this paper; I first review the key ethical issues that have been addressed in this debate. Although there is an emerging consensus now that research on the editing of human somatic cells for therapeutic purpose should be pursued further; the prospect of using gene-editing techniques for (...) the purpose of human enhancement has been met with strong criticism. The main thesis that I defend in this paper is that some of the most vocal objections recently raised against the prospect of genetic human enhancement are not justified. I put forward two arguments for the morality of genetic human enhancement. The first argument shows how the moral and legal framework within which we currently claim our procreative rights; especially in the context of IVF procedures; could be deployed in the assessment of the morality and legality of genetic human enhancement. The second argument calls into question the assumption that the average level of human cognitive performance should have a normative character. (shrink)

With recent reports that a Chinese scientist used CRISPR-Cas9 to heritably edit the genomes of human embryos (i.e., germline editing) brought to term, discussions regarding the ethics of the technology are urgently needed. Although certain applications of germline editing have been endorsed by both the National Academy of Sciences (US) and the Nuffield Council (UK), this paper explores the ethical concerns related even to such therapeutic uses of the technology. Additionally, this paper questions whether the technology could ever feasibly be (...) contained to the therapeutic realm. Consequently, this paper necessarily considers the ethical concerns related to enhancement uses of the technology even if only therapeutic applications are initially considered. In light of the concomitant risks, this paper assesses the technology’s countervailing benefits to conclude they do not prevail given that similar outcomes can largely be achieved with existing technologies. Consequently, this paper recommends an international ban on germline editing. (shrink)

Large deletions and genomic re‐arrangements are increasingly recognized as common products of double‐strand break repair at Clustered Regularly Interspaced, Short Palindromic Repeats ‐ CRISPR associated protein 9 (CRISPR/Cas9) on‐target sites. Together with well‐known off‐target editing products from Cas9 target misrecognition, these are important limitations, that need to be addressed. Rigorous assessment of Cas9‐editing is necessary to ensure validity of observed phenotypes in Cas9‐edited cell‐lines and model organisms. Here the mechanisms of Cas9 specificity, and strategies to assess and mitigate unwanted effects (...) of Cas9 editing are reviewed; covering guide‐RNA design, RNA modifications, Cas9 modifications, control of Cas9 activity; computational prediction for off‐targets, and experimental methods for detecting Cas9 cleavage. Although recognition of the prevalence of on‐ and off‐target effects of Cas9 editing has increased in recent years, broader uptake across the gene editing community will be important in determining the specificity of Cas9 across diverse applications and organisms. (shrink)

The field of genetics has seen major advances in recent decades, particularly in research, prevention and diagnosis. One of the most recent developments, the genomic editing technique Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, has opened the possibility for genetic therapies through genome modification. The technique marks an improvement on previous procedures but poses some serious ethical conflicts. Bioethics is the discipline geared at finding answers to ethical challenges posed by progress in medicine and biology and examining their repercussions for (...) society. It can also offer a conceptualization of these ethical dilemmas. The aim of this paper is to offer a map of the ethical dilemmas associated with this technique by way of a critical analysis of current literature. The main issues can be grouped in four areas: efficacy and security; the types of cells which can be targeted by the technique (somatic, embryonic and gametes); the goal of the therapy; and accessibility and justice. (shrink)

Dieses Buch befasst sich mit der rechtlichen Bewertung von modernen Verfahren der Intervention in die menschliche Keimbahn, d.h. von gentechnischen Veränderungen am Menschen, die an die nachfolgenden Generationen weitergegeben werden. Neuartige Methoden wie die CRISPR/Cas9-Technik, der Mitochondrientransfer und die Möglichkeit der Herstellung artifizieller Gameten aus hiPS-Zellen stellen das Recht vor neue Herausforderungen. Insbesondere ist fraglich, ob die aktuell bestehenden Gesetze diese neuen Verfahren noch erfassen oder ob gesetzliche Lücken entstanden sind. Dieses Buch analysiert in diesem Zusammenhang die Rechtslage in Deutschland (...) und Frankreich. Es behandelt dabei sowohl genetische Veränderungen an menschlichen Keimbahnzellen zur Forschung in vitro als auch solche, die in der Geburt von Menschen münden. Zudem wird der Frage nachgegangen, ob das deutsche Verfassungsrecht einer Anwendung dieser Verfahren grundsätzlich entgegensteht oder ob eine gesetzliche Zulassung in der Zukunft unter bestimmten Voraussetzungen möglich wäre. Auf der Grundlage des Rechtsvergleichs sowie der verfassungsrechtlichen Untersuchung formuliert das Buch einen Regelungsvorschlag, sowohl zur Beseitigung aktuell bestehender rechtlicher Lücken und Unklarheiten als auch im Hinblick auf eine mögliche Anwendung der Verfahren. (shrink)

BackgroundCRISPR-Cas9, a technology enabling modification of the human genome, is developing rapidly. There have been calls for public debate to discuss its ethics, societal implications, and governance. So far, however, little is known about public attitudes on CRISPR-Cas9. This study contributes to a better understanding of public perspectives by exploring the various holistic perspectives Dutch citizens have on CRISPR-Cas9.MethodsThis study used Q methodology to identify different perspectives of Dutch citizens (N = 30) on the use of CRISPR-Cas9. The Q-sort method (...) aims at segmenting audiences based on the structural characteristics of their perspectives. Participants individually ranked 32 statements about CRISPR-Cas9 and discussed their rankings in small groups. By-person factor analysis was performed using PQMethod. Participants’ contributions to the discussions were used to further make sense of the audience segments identified.ResultsFive perspectives on CRISPR-Cas9 were identified: (1) pragmatic optimism (2) concerned scepticism; (3) normative optimism; (4) enthusiastic support; and (5) benevolent generalism. Each perspective represents a unique position motivated by different ranking rationales. Sorting rationales included improving health, preventing negative impacts on society, and fear of a slippery slope. Overall, there is broad, but not universal support for medical uses of CRISPR-Cas9.ConclusionsResearch on CRISPR-Cas9 should prioritise the broadly supported applications of the technology. Research and public debates on CRISPR-Cas9, its uses, its broader implications, and the governance of CRISPR-Cas9 are recommended. A discourse that includes all perspectives can contribute to the embedding of future uses of CRISPR-Cas9 in society. This study shows that Q methodology followed by group discussions enables citizens to contribute meaningfully to discourses about research. (shrink)

Genome editing holds the promise of revolutionizing many fields in which human interventions have hitherto proved to be insufficient to meet major global challenges, like nutrition and environmental protection. However, it is controversial how far this method might also be applied to the human germline with a view to preventing the transmission of serious genetic diseases to offspring. While there is a near-consensus that genome editing, at the present stage of science, should not be applied clinically, it is unclear whether (...) this also extends to clinically oriented research. It is argued that among the arguments against interventions in the human germline there is only one that is sufficiently strong to be practically relevant: The argument that it is doubtful whether the challenge of off-target effects with potentially fatal health consequences can be met. Since nearly all objectives of human germline genome editing can be attained by PGD, there are good grounds for directing clinically oriented research toward the improvement of this alternative method, which has been proven to be without substantial risks and which involves no ethical problems over and above those involved in genome editing. (shrink)

La aparición de las modernas técnicas de modificación genética (CRISPRCas9) ha abierto maravillosas expectativas en el campo de la biomedicina. Sin embargo, su aplicación sobre la línea germinal humana despierta todavía una fuerte oposición por parte de amplios colectivos. A menudo se aduce que factores como el riesgo que implica esta técnica, su propia futilidad, la amenaza implícita a la integridad del genoma humano, o la posibilidad de que acaben dando naturaleza a una nueva eugenesia justifican la necesidad de trazar (...) una prohibición o, al menos, una moratoria sobre ellas. En este texto debatiremos la solvencia de cada uno de estos argumentos, concluyendo que, en realidad, no hay buenos motivos para oponerse a la técnica que nos ocupa. (shrink)

Given recent advancements in CRISPR‐Cas9 powered genetic modification of gametes and embryos, both popular media and scientific articles are hailing CRISPR’s life‐saving, curative potential for people with serious monogenic diseases. But claims that CRISPR modification of gametes or embryos, a form of germline engineering, has therapeutic value are deeply mistaken. This article explains why reproductive uses of CRISPR, and germline engineering more generally, do not treat or save lives that would otherwise have a genetic disease. Reproductive uses of CRISPR (...) create healthy people whose existence is not inevitable in the first place. Creating healthy lives has distinct and lesser moral value from saving or curing lives that would otherwise have genetic disease. The real value in reproductive uses of CRISPR is in helping a very limited population of people have healthy, genetically related children. This diminished value cannot compete with the concerns in opposition to germline engineering, nor is it worth the investment of research money. (shrink)

CRISPR Cas9-powered gene drive allows for the rapid alteration of malaria-causing mosquitoes to spread an infertility gene or resistance to malaria among their species. Malaria eradication would be a great boon to human health. But many are concerned with driving genetic changes through a natural species. This chapter catalogs objections to the use of gene drive in mosquitoes for eradicating malaria. In-principle objections to gene drive use are not compelling. The most urgent concerns are related to the safety of the (...) technology for the environment and human health. Philosophers play a critical role in working along scientists to develop risk/benefit models that weigh the reasons for and against gene drive to eradicate malaria based on our best scientific knowledge and rigorous normative reasoning. (shrink)

This essay focuses on possible nonhuman applications of CRISPR/Cas9 that are likely to be widely overlooked because they are unexpected and, in some cases, perhaps even “frivolous.” We look at five uses for “CRISPR Critters”: wild de-extinction, domestic de-extinction, personal whim, art, and novel forms of disease prevention. We then discuss the current regulatory framework and its possible limitations in those contexts. We end with questions about some deeper issues raised by the increased human control over life on earth offered (...) by genome editing. (shrink)

The Cas9 endonuclease is the central component of the Type II CRISPR/Cas system, a prokaryotic adaptive restriction system against invading nucleic acids, such as those originating from bacteriophages and plasmids. Recently, this RNA‐directed DNA endonuclease has been harnessed to target DNA sequences of interest. Here, we review the development of Cas9 as an important tool to not only edit the genomes of a number of different prokaryotic and eukaryotic species, but also as an efficient system for site‐specific transcriptional repression or (...) activation. Additionally, a specific Cas9 protein has been observed to target an RNA substrate, suggesting that Cas9 may have the ability to be programmed to target RNA as well. Cas proteins from other CRISPR/Cas subtypes may also be exploited in this regard. Thus, CRISPR/Cas systems represent an effective and versatile biotechnological tool, which will have significant impact on future advancements in genome engineering. (shrink)

In this pivotal year for gene editing, the breakthrough molecular system CRISPR–Cas9 has advanced on three fronts. In under seven months, an influential scientific body—the National Academies of Sciences, Engineering, and Medicine the National Academies of Sciences, Engineering, and Medicine—cracked open the door to human germline gene editing, ownership of patents covering CRISPR–Cas9 came into much sharper focus as a result of a dispute between two parties, and experiments showing proof of concept of the most controversial of uses—altering germlines of (...) humans—were revealed as having been successfully performed by a mainstream laboratory. Given the vast spoils that await the patent owners, final results of all patent disputes over CRISPR–Cas9 patents may stretch on for years. Meanwhile, bioethical considerations of CRISPR–Cas9 have also been contentious as the United States and other countries grapple with how best to regulate gene editing. (shrink)

The emergence of CRISPR/Cas9 technology has revolutionized gene editing and made both gene therapy and eugenic control of future human evolution plausible. This accessible book puts these developments in their historical and scientific contexts and analyzes the policy and ethical challenges they raise. It presents the case for altering the human germ-line to eliminate a large number of genetic diseases controlled by a single or few genes, while pointing out that gene therapy is likely to ineffective for diseases with more (...) complex causation. In parallel it explores the possibility of genetic enhancement in a similarly subscribed set of cases. But it also argues that, in general, genetic enhancement is ethically problematic and should be approached with caution. Given the success of CRISPR/Cas9 gene editing, and the explosion of related techniques, in practice it would be virtually impossible to ban germ-line editing for the future. A more useful goal is to regulate it with oversight that represents all stakeholders. That, in turn, requires an informed public discussion of these issues which this book aims to foster. (shrink)

En 2016 se hizo pública una nueva técnica para editar genes: la CRISPR-Cas9. Cinco años después es posible dar una mirada que desde la Bioética examine el desarrollo de esta biotecnología. Es constatable que la técnica de edición de genes en la línea somáticas se ha difundido y está empezando a mostrar algunos resultados. Sin embargo, a pesar de ellos no es posible extender ese trabajo a las líneas germinales a través de la edición hereditaria del genoma humano. Se estudian (...) dos documentos, el informe de la Comisión Internacional para el Uso Clínico de la Edición del Genoma Humano (2020) y el informe de recomendaciones del Comité Asesor de Expertos en el Desarrollo de Estándares Globales para la Gobernanza y Supervisión de la Edición del Genoma Humano de la Organización Mundial de la Salud (2021) y se reflexiona sobre su contenido y sus consecuencias. (shrink)

The bioethical principle of autonomy is problematic regarding the future of the embryo who lacks the ability to self-advocate but will develop this defining human capacity in time. Recent experiments explore the use of clustered regularly interspaced short palindromic repeats /Cas9 for germline engineering in the embryo, which alters future generations. The embryo’s inability to express an autonomous decision is an obvious bioethical challenge of germline engineering. The philosopher Joel Feinberg acknowledged that autonomy is developing in children. He advocated that (...) to reserve this future autonomy, parents should be guided to make ethical decisions that provide children with open futures. Here, Feinberg’s 1980 open future theory is extended to the human embryo in the context of CRISPR germline engineering. Although the embryo does not possess the autonomous decision-making capacity at the time of germline engineering, the parental decision to permanently change the unique genetic fabric of the embryo and subsequent generations disregards future autonomy. Therefore, germline engineering in many instances is objectionable considering Feinberg’s open future theory. (shrink)

This paper presents an overview of the key ethical questions of performing gene editing research on military service members. The recent technological advance in gene editing capabilities provided by CRISPR/Cas9 and their path towards first-in-human trials has reinvigorated the debate on human enhancement for non-medical purposes. Human performance optimization has long been a priority of military research in order to close the gap between the advancement of warfare and the limitations of human actors. In spite of this focus on temporary (...) performance improvement, biomedical enhancement is an extension of these endeavours and the ethical issues of such research should be considered. In this paper, we explore possible applications of CRISPR to military human gene editing research and how it could be specifically applied towards protection of service members against biological or chemical weapons. We analyse three normative areas including risk–benefit analysis, informed consent, and inequality of access as it relates to CRISPR applications for military research to help inform and provide considerations for military institutional review boards and policymakers. (shrink)

When the use of CRIsPR-Cas9 to edit DNA was first reported in 2012, it was quickly heralded by scientists, policymakers, and journalists as a transformative technology. CRISPR-Cas9 provides the means to change DNA in ways that either were not generally possible using previous genetic technologies or that were orders of magnitude more laborious or inefficient to undertake. CRISPR's possible applications were readily apparent and seemingly endless, from supercharging laboratory research to modifying insects that transmit disease to eliminating genetic conditions. By (...) 2015, Wired magazine was calling the discovery "The Genesis Engine."Against a backdrop of disappointing results from gene transfer... (shrink)

The Streptococcus pyogenes CRISPR‐Cas system has gained widespread application as a genome editing and gene regulation tool as simultaneous cellular delivery of the Cas9 protein and guide RNAs enables recognition of specific DNA sequences. The recent discovery that Cas9 can also bind and cleave RNA in an RNA‐programmable manner indicates the potential utility of this system as a universal nucleic acid‐recognition technology. RNA‐targeted Cas9 (RCas9) could allow identification and manipulation of RNA substrates in live cells, empowering the study of cellular (...) gene expression, and could ultimately spawn patient‐ and disease‐specific diagnostic and therapeutic tools. Here we describe the development of RCas9 and compare it to previous methods for RNA targeting, including engineered RNA‐binding proteins and other types of CRISPR‐Cas systems. We discuss potential uses ranging from live imaging of transcriptional dynamics to patient‐specific therapies and applications in synthetic biology. (shrink)

In the last 10 years, we have witnessed a blooming of targeted genome editing systems and applications. The area was revolutionized by the discovery and characterization of the transcription activator‐like effector proteins, which are easier to engineer to target new DNA sequences than the previously available DNA binding templates, zinc fingers and meganucleases. Recently, the area experimented a quantum leap because of the introduction of the clustered regularly interspaced short palindromic repeats (CRISPR)‐associated protein (Cas) system (clustered regularly interspaced short palindromic (...) sequence). This ribonucleoprotein complex protects bacteria from invading DNAs, and it was adapted to be used in genome editing. The CRISPR ribonucleic acid (RNA) molecule guides to the specific DNA site the Cas9 nuclease to cleave the DNA target. Two years and more than 1000 publications later, the CRISPR‐Cas system has become the main tool for genome editing in many laboratories. Currently the targeted genome editing technology has been used in many fields and may be a possible approach for human gene therapy. Furthermore, it can also be used to modifying the genomes of model organisms for studying human pathways or to improve key organisms for biotechnological applications, such as plants, livestock genome as well as yeasts and bacterial strains. (shrink)

The emergence of CRISPR/Cas9 technology has revolutionized gene editing and made both gene therapy and eugenic control of future human evolution plausible. This accessible book puts these developments in their historical and scientific contexts and analyzes the policy and ethical challenges they raise. It presents the case for altering the human germ-line to eliminate a large number of genetic diseases controlled by a single or few genes, while pointing out that gene therapy is likely to ineffective for diseases with more (...) complex causation. In parallel it explores the possibility of genetic enhancement in a similarly subscribed set of cases. But it also argues that, in general, genetic enhancement is ethically problematic and should be approached with caution. Given the success of CRISPR/Cas9 gene editing, and the explosion of related techniques, in practice it would be virtually impossible to ban germ-line editing for the future. A more useful goal is to regulate it with oversight that represents all stakeholders. That, in turn, requires an informed public discussion of these issues which this book aims to foster. (shrink)

In 2012, a new and promising gene manipulation technique, CRISPR-Cas9, was announced that seems likely to be a foundational technique in health care and agriculture. However, patents have been granted. As with other technological developments, there are concerns of social justice regarding inequalities in access. Given the technologies’ “foundational” nature and societal impact, it is vital for such concerns to be translated into workable recommendations for policymakers and legislators. Colin Farrelly has proposed a moral justification for the use of patents (...) to speed up the arrival of technology by encouraging innovation and investment. While sympathetic to his argument, this article highlights a number of problems. By examining the role of patents in CRISPR and in two previous foundational technologies, we make some recommendations for realistic and workable guidelines for patenting and licensing. (shrink)

This paper seeks to expand our appreciation of the gene editing tool, clustered regularly interspaced short palindromic repeats‐associated protein 9 (CRISPR‐Cas9), its function, its benefits and risks, and the challenges of regulating its use. I frame CRISPR's emergence and its current use in the context of 150 years of formal exploration of heredity and genetics. I describe CRISPR's structure and explain how it functions as a useful engineering tool. The contemporary international and domestic regulatory environment governing human genetic interventions (...) is reviewed and shown to be increasingly ineffective in its ability to restrain, guide, and optimize the emerging use of CRISPR. Several reasons for this lack of consensus are discussed. In conclusion, I suggest a number of public policy recommendations that might allow us to simultaneously embrace our most important moral values and manage the inevitable power CRISPR will come to have in our lives. (shrink)

The ease and applicability of CRISPR/Cas9––a new and precise gene editing and reproductive technology––have garnered hype and heightened concern about its potential ‘unprecedented and horrific consequences’ and have led many scientific leaders to call for a moratorium on its research and use. CRISPR appears distinctly more controversial than previous technological innovations, with a greater reach and speed of human treatment and enhancement; however, we have seen similarly inflated hopes and fears in response to other medical innovations for well over a (...) century. One intervention that has both historically and recently incited alarm––vaccines––serves as a pertinent example of what could go wrong if a technology's reach is shortened due to inflated fears. By comparing the vaccine controversy and the CRISPR debate, we can help separate the hype from the realistic potential of these technologies. How our society grapples with such innovations will determine the extent to which their impact on our individual and collective health will be beneficial. We must recognise the need for a tempered approach to CRISPR conversation leading to regulation and ethical application. Although CRISPR's reach will continue expanding with ongoing research, thus requiring continuous evaluation, the lessons we have learned from the vaccine controversy demonstrate that our approach must not be to shut down regulation and application now, but to thoughtfully conjoin productive debate and action so that therapeutic gene editing can alleviate suffering as soon as possible without precipitating social outcomes we would belatedly deplore. (shrink)

As i was finalizing this introduction to the Special Issue on CRISPR genome editing for Perspectives in Biology and Medicine, news broke that the Chinese scientist He Jiankui had been sentenced in Chinese court to three years in prison for "illegal medical practice" for his role in the creation of the world's first genome-edited babies. This official reprimand reinforced the worldwide condemnation and censure that followed He's announcement in November 2018 that his team at the Southern University of Science and (...) Technology in Shenzhen, China, had used the CRISPR-Cas9 genome-editing tools on human embryos created via in vitro fertilization. He produced and brought to term two babies carrying... (shrink)

This editorial provides an ethical analysis of the consent materials and other documents relating to the recent creation and birth of twin girls who had their genes edited using CRISPR-cas9 in a controversial Chinese research study. It also examines the “draft ethical principles” published by the leader of the research study. The results of the analysis further intensify serious ethical concerns about the conduct of this study.

Gene drives are selfish genetic elements that use a variety of mechanisms to ensure they are transmitted to subsequent generations at greater than expected frequencies. Synthetic gene drives based on the clustered regularly interspersed palindromic repeats genome editing system have been proposed as a way to alter the genetic characteristics of natural populations of organisms relevant to the goals of public health, conservation, and agriculture. Here, we review the principles and potential applications of CRISPR drives, as well as means proposed (...) to prevent their uncontrolled spread. We also focus on recent work suggesting that factors such as natural genetic variation and inbreeding may represent substantial impediments to the propagation of CRISPR drives. CRISPR-based synthetic selfish genetic elements, or gene drives, have been proposed as a means by which to genetically alter natural populations to address issues in agriculture, conservation, and public health. We describe key concepts of CRISPR gene drives and limitations that must be addressed before their use in the wild. (shrink)

Les sciences en général, et les sciences de la vie en particulier, ont un tel impact sur le quotidien des personnes que les scientifiques ont un devoir d’anticipation. Probablement en raison de sa fonction si particulière de support de l’information héréditaire, l’ADN, sa caractérisation, son décryptage, ses modifications, ont été l’objet d’une attention particulière depuis une cinquantaine d’années. C’est de nouveau le cas depuis la découverte puis l’adaptation récente des techniques de modifications ciblées du génome. Des découvertes scientifiques ont lieu (...) chaque jour, elles font rarement la une de l’actualité même si régulièrement des média en manque de sensations fortes nous annoncent une nouvelle révolution. Mais la réalité pratique est rare parce que les découvertes qui amènent à un changement de paradigme sont rares. C’est parce qu’une découverte académique donne rarement lieu à une application technologique et que même si celle-ci est envisagée, le transfert est long, difficile et peu souvent couronné de succès. Il est donc d’autant plus nécessaire aujourd’hui de souligner que c’est à l’une de ces révolutions technologiques que nous assistons avec la nouvelle maîtrise de modifications ciblées du génome grâce au système CRISPR-Cas9 et à ses dérivés. Les enjeux scientifiques et médicaux mais également économiques et environnementaux sont énormes. Il convient donc d’évaluer au plus vite le cadre légal, éthique et sociétal permettant de bénéficier au mieux de ces techniques sans en subir les dangers. Seul un cadre international associant une expertise scientifique pluridisciplinaire à la gouvernance est envisageable, c’est donc à la création d’un Groupe International d’Experts du Génome que nous appelons. Pour ce faire une première position de consensus européen a été élaborée et mise en discussion lors de plusieurs colloques internationaux. (shrink)

Los teóricos que defienden las técnicas de modificación genética sin algún conservadurismo argumentan que éstas aumentarán nuestras capacidades y, también, evitarán el dolor innecesario junto con algunos tipos de sufrimiento humano. Autores transhumanistas como Nick Bostrom, Natasha Vita-More y Max More, no sólo minusvaloran los riesgos del uso de biotecnología –así como la técnica CRISPR-CAS9–, sino que asumen que vivir una vida humana plena se relaciona en proporción directa con el pleno gozo de nuestras habilidades físicas e intelectuales y con (...) la ausencia de dolor o sufrimiento. No obstante, la visión de algunos teóricos sobre la discapacidad como Fiona Campbell, Elizabeth Barnes y Bárbara Arneil, insisten en que las limitaciones humanas no deberían ser vistas de manera trágica o como una desgracia; al contrario, argumentan que es posible vivir plenamente desde la diversidad funcional (o discapacidad). Por tanto, en este artículo ponemos a prueba ambos supuestos, a partir de la idea de discapacidad y, así, mostraremos si es que la felicidad depende fuertemente de la funcionalidad del cuerpo humano. (shrink)

A global socio‐bioethics is called upon to address the ethical challenges arising from the revolutionary gene editing technologies such as CRISPR‐Cas9, which offers the capability to rewrite the human genome. The ethical inquiry Françoise Baylis has undertaken in the book Altered Inheritance: CRISPR and the Ethics of Human Genome Editing (Harvard University Press, 2019) operates at individual, societal and global levels. Baylis has not only presented insights on how to practice “slow science” and achieve broad societal consensus through empowering (...) the public, but she also shown what a global socio‐bioethics approach can offer for the further development of bioethics. (shrink)