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Ethics of Human Genome Editing
Abstract
Advances in human genome editing, in particular the development of the clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 method, have led to increasing concerns about the ethics of editing the human genome. In response, the US National Academy of Sciences and the National Academy of Medicine constituted a multidisciplinary, international committee to review the current status and make recommendations. I was a member of that committee, and the core of this review reflects the committee's conclusions. The committee's report, issued in February 2017, recommends the application of current ethical and regulatory standards for gene therapy to somatic (nonheritable) human genome editing. It also recommends allowing experimental germline genome editing to proceed if (a) it is restricted to preventing transmission of a serious disease or condition, (b) the edit is a modification to a common DNA sequence known not to be associated with disease, and (c) the research is conducted under a stringent set of ethical and regulatory requirements. Crossing the so-called red line of germline genome editing raises important bioethical issues, most importantly, serious concern about the potential negative impact on individuals with disabilities. This review highlights some of the major ethical considerations in human genome editing in light of the report's recommendations.
... Some now well-established uses of somatic cell modification have been translated without significant bioethical demurral, usually where both a specific medical benefit and a favourable risk-benefit ratio obtains (Coller, 2019). Such is the case in allogeneic (donor-facilitated) hematopoietic stem cell transplantation, which involves the modification of a patient's DNA through the infusion of exogenous DNA from donor cells, creating true biological chimeras (Themeli et al., 2011). ...
... A third route, in which edited somatic cells may be administered to fetuses (in utero), is also under investigation . In utero SCGE may offer transformative therapeutic benefits where an unborn child, through prenatal genetic testing, is diagnosed with a monogenic disease that would be irreversible or untreatable after birth, such as inborn errors of metabolism (Houtkooper, 2018;World Health Organization, 2021a;Coller, 2019;Hartman et al., 2018). However, in utero editing may also pose increased risks of germline modifications if the germ cells have not been entirely sequestered from the somatic cells (Coller, 2019). ...
... In utero SCGE may offer transformative therapeutic benefits where an unborn child, through prenatal genetic testing, is diagnosed with a monogenic disease that would be irreversible or untreatable after birth, such as inborn errors of metabolism (Houtkooper, 2018;World Health Organization, 2021a;Coller, 2019;Hartman et al., 2018). However, in utero editing may also pose increased risks of germline modifications if the germ cells have not been entirely sequestered from the somatic cells (Coller, 2019). ...
Somatic cell genome editing (SCGE) now allows exquisitely precise and targeted non-heritable changes to be made to human DNA. While SCGE has many possible applications, clinical trials indicate its great potential to provide new forms of medical treatment, as well as cures, for a range of prevalent monogenic diseases, including several disorders of the blood (hemoglobinopathies). This chapter provides an overview of the nature of somatic cells, a discussion of their connection with genetic disease, and a summary of the bioethical issues that attend various therapeutic uses of the system. The chapter takes sickle-cell disease as a case study, identifying the advantages that SCGE promises over the current best treatment, as well as the issues that will likely compel patients, clinicians and others to engage in difficult bioethical decision-making. Lastly, the chapter takes up four bioethical principles—nonmaleficence, beneficence, autonomy and justice—to analyze some of the most pressing bioethical issues associated with SCGE, as well as recent recommendations for governing the technology published by the World Health Organization.KeywordsSomatic cell genome editingSickle-cell diseaseProgrammable nuclease-mediated SCGEBioethics of SCGEGene therapy
... In contrast to our medical orientation, which leads us to believe that DNA mutations are harmful to our health, evolutionary biology believes that they are essential for our species' survival in the current environment or adaptation to shifting environments. Mutations, then, are not faults or a reflection of the replication molecular machinery's infidelity, but rather a fundamental and important component of our species' evolutionary progress (Coller, 2019). ...
... It is unknown whether modified organisms will continue to be affected completely and whether and to what extent edited genes will be passed on to future generations, adversely impacting them in unexpected ways. A precise risk-benefit analysis is thus significantly complicated, not only due to technical constraints, but also due to the inherent complexities of biological systems (Coller, 2019). ...
... Individuals with genetic abnormalities that have atypical phenotypes have historically been stigmatized, bullied, discriminated against, and even physically harmed. Such treatment can have a significant psychological impact on those with the diseases, particularly children, by eliciting emotions of insecurity and anxiety about one's self-image and self-worth, which frequently result in social isolation (Coller, 2019). Nowadays, public accommodations and education have significantly improved conditions for people with genetic abnormalities that impair their ability to operate normally, both in schools and at work (Global Genes, 2020;Sundar, 2017). ...
... Thus, genome editing research is being conducted widely across many countries, including efforts to understand potential application in altering the genome of human embryos [1,2]. However, concession for its use on human embryos still has various unresolved technological and ethical considerations despite its legitimate potential for promoting health and preventing disease [3,4]. ...
... In our study, the percentage agreeing to its use was about 60% at most, suggesting that differences may be influenced by country-specific characteristics and cultural background; approximately 80% to 90% of the participants in Jedweb's study was from the United States, Australia, Canada, and United Kingdom. In contrast to our study which included only Japanese, the higher percentage reported in the previous multi-national study may be a reflection of influences originating from various ethnicities, religions, and cultural spheres [4,22]. With regard to enhancement, all groups showed a high percentage of disagreement with the use of genome editing on human embryos. ...
Recent advances in genome editing technology are accompanied by increasing public expectations on its potential clinical application, but there are still scientific, ethical, and social considerations that require resolution. In Japan, discussions pertaining to the clinical use of genome editing in human embryos are underway. However, understanding of the public’s sentiment and attitude towards this technology is limited which is important to help guide the debate for prioritizing policies and regulatory necessities. Thus, we conducted a cross-sectional study and administered an online questionnaire across three stakeholder groups: the general public, patients and their families, and health care providers. We received responses from a total of 3,511 individuals, and the attitudes were summarized and compared among the stakeholders. Based on the distribution of responses, health care providers tended to be cautious and reluctant about the clinical use of genome editing, while patients and families appeared supportive and positive. The majority of the participants were against the use of genome editing for enhancement purposes. Participants expressed the view that clinical use may be acceptable when genome editing is the fundamental treatment, the risks are negligible, and the safety of the technology is demonstrated in human embryos. Our findings suggest differences in attitudes toward the clinical use of genome editing across stakeholder groups. Taking into account the diversity of the public’s awareness and incorporating the opinion of the population is important. Further information dissemination and educational efforts are needed to support the formation of the public’s opinion.
... Driven by technology development, updates to the genetic firmware, e.g., via gene editing, will inevitably be considered and attempts will be likely made. A recent report on the human genome editing "supports crossing what has been a bright red line by recommending that clinical trials of heritable human genome editing be allowed" to prevent "a serious disease or condition" [180]. Without doubt, psychiatric disorders, including addiction, are "serious" despite their fuzzy diagnostic thresholds. ...
... Hence, failure to protect personal safety, evinced as risky sexual behavior, may have its origins during a stressful childhood. Notably, stressors such as maltreatment in early childhood potentiate risk of developing ADHD in childhood which shares genetic risk with addiction and increases the probability of early age onset AC use and risk for addiction [179,180]. Notably, a history of maltreatment is associated with reduced performance on tests measuring executive cognitive capacities in children [170] and adolescents [168]. In effect, the capacity to acquire an executive control system to modulate behavior and emotions during social interactions is compromised. ...
Drug addiction is a devastating mental health problem with an alarming increasing prevalence. Underlining biological mechanisms of drug addiction are abnormal neuronal and brain activity following acute and repeated drug exposures. Altered gene-expression patterns are found in reward-related brain regions of drug addicts and in animal models. These changes in gene expression are responsible for morphological and molecular abnormalities in reward-related brain regions. Epigenetic modifications such as DNA (hydroxy)methylation and histone mark modifications are upstream regulators of gene expression. Global and site-specific changes in epigenetic markers are observed in addiction. Here, we discuss recent findings linking epigenetic changes to drug addiction in both animal and human studies. We will speculate on potential directions for diagnosis and therapeutics of drug addiction using epigenetic screening and epigenetic-modifying drugs.KeywordsEpigeneticsHistone modificationsDNA methylationDrug abuseAddiction
... In general, germline genome editing's ethical issues can be classified into those arising from its potential failure and success (Ormond et al., 2017;Coller, 2019). Firstly, the potential harm is perceived as a risk that does not outweigh the potential benefits. ...
... There are significant concerns about eugenics, social justice, and equal access to therapy (Coller, 2019). Eugenics is a concept that retains positive traits and removes negative characteristics. ...
Gene editing platforms have revolutionized the field of genetics with a direct impact on the public health system. Although there are apparent benefits, it is often accompanied by public debates over its uncertainties and risks. In the Malaysian context, modern biotechnology has raised questions about how to best govern gene editing in regulations, biosafety, and biosecurity. Even though standards and guidelines on stem cell and cell-based therapies have been developed, there are no appropriate legal frameworks available for gene editing yet. Nevertheless, biosafety regulations were established to balance promoting biotechnology and protecting against their potential environmental and human health risks. There is also a need to address the potential of genetically modified organisms (GMOs) as bioweapons. Numerous frameworks from several international organizations may provide valuable input in formulating documents on gene editing. By establishing comprehensive guidelines, legal policies, and standards to tackle the challenges and risks associated with gene editing, Malaysia can successfully apply this modern technology in this country.
... Therefore, for objective reasons, experiments with the genome and genes are not harmless -neither of a neutral, nor of a unequivocally positive nature -at least in terms of ensuring biological safety and biological diversity (Baker, 2016;Coller, 2019). It is also impossible to disregard the subjective factors -socio-cultural, religious and other attitudes on the part of the population, which, on the whole, is wary of any experiments with living matter. ...
The principle of inviolability of the human genome is discussed in the context of biomedicine and related areas. The ‘pros’ and ‘cons’ of interference in the human genome are presented in terms of somatic and germ cells, as well as those interventions affecting the human genome at the embryonic stage of development. In connection with the development of synthetic biology, the human genome, as well as its fragments, genes, and genetic information, is increasingly becoming of practical interest for various parties (entities and individuals), and, therefore, need protection, including legal protection. From a systemic approach, the principle of inviolability of the human genome cannot be absolute. The limits of its applicability (force and effect) can be affected by: the degree of development of genetic and information technologies; availability of effective institutions for control over modern technologies; functioning of the mechanisms ensuring biological, information and other types of security; national, cultural, religious peculiarities; established legal and ethical traditions, and practices in a number of sectors and fields of activity (research, medicine, information, etc.).
... For those disorders with an identified genetic cause, research has been focused on gene therapy approaches, with mixed outcomes (3,4). Importantly, technical and ethical questions regarding these strategies are likely to hinder and delay their use in the near future (5,6). Therefore, other lines of research should, perhaps, focus on complementary or alternative approaches that may be more feasible. ...
Spinocerebellar ataxia type 3 (SCA3) is an adult-onset neurodegenerative disease caused by a polyglutamine expansion in the ataxin-3 (ATXN3) gene. No effective treatment is available for this disorder, other than symptom-directed approaches. Bile acids have shown therapeutic efficacy in neurodegenerative disease models. Here, we pinpointed tauroursodeoxycholic acid (TUDCA) as an efficient therapeutic, improving the motor and neuropathological phenotype of SCA3 nematode and mouse models. Surprisingly, transcriptomic and functional in vivo data showed that TUDCA acts in neuronal tissue through the glucocorticoid receptor (GR), but independently of its canonical receptor, the FXR. TUDCA was predicted to bind to the GR, similarly to corticosteroid molecules. GR levels were decreased in disease-affected brain regions, likely due to increased protein degradation as a consequence of ATXN3 dysfunction, being restored by TUDCA treatment. Analysis of a SCA3 clinical cohort showed intriguing correlations between the peripheral expression of GR and the predicted age at disease onset, in pre-symptomatic subjects, and of FKBP5 expression with disease progression, suggesting this pathway as a potential source of biomarkers for future study. We have established a novel in vivo mechanism for the neuroprotective effects of TUDCA in SCA3, and propose this readily available drug for clinical trials in SCA3 patients.
... Informed consent is essential to safeguard an ethical and legal requirement for research and for the participant to understand and voluntarily confirm their willingness for the trial. 143 In Malaysia, practitioners and patients have an observable discrepancy in understanding the consent form. 144 The patients showed a lack of understanding of the consent information, while the practitioners tended to overlook the signed consent as patients fully understood the issue in question. ...
A new era of gene and cell therapy for treating human diseases has been envisioned for several decades. However, given that the technology can alter any DNA/cell in human beings, it poses specific ethical, legal, and social difficulties in its application. In Malaysia, current bioethics and medical ethics guidelines tackle clinical trials and biomedical research, medical genetic services, and stem cell research/therapy. However, no comprehensive framework and policy is available to cater to ethical gene and cell therapy in the country. Incorporating ethical, legal, and social implications (ELSI) would be crucial to guide the appropriate use of human gene and cell therapy in conjunction with precision medicine. Policy experts, scientists, bioethicists, and public members must debate the associated ELSI and the professional code of conduct while preserving human rights.
... For those that recorded a religious affiliation, it was observed that Muslims were more likely to vote against gene editing because they feel it goes against their religion. In other words, as described in Pew's study in 2016, it is feared that one is meddling with nature or God's creation (Coller 2019;Funk et al. 2016). Evaluating the knowledge, attitude, and perception of members of the health sector and bio-scientists on the application of genomic/mitochondria modification for gene therapy (Fig. 2) is equally important especially since they are the front liners and potentially have adequate knowledge of the benefits/risks of the biotechnologies in question. ...
Gene editing and mitochondrial replacement therapy (MRT) are biotechnologies used to modify the host nuclear and mitochondrial DNA, respectively. Gene editing is the modification of a region of the host genome using site-specific nucleases, in particular the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system. Heritable and somatic genome editing (HGE and SGE) are used in gene therapy. MRT is a technique used to substitute the defective mitochondria in the recipient embryo with a female donor healthy mitochondrion in order to prevent the inheritance of mothers’ defective mitochondria resulting in the change of mitochondria of the entire generation to come. To evaluate the perception of the Nigerian citizens on human genome modification, two survey forms were created and distributed in-person and majorly online. There was a total of 268 responses, 188 from the public and 80 from health workers and bio-scientists. The results showed poor knowledge about gene editing and MRT by the Nigerian public, but its use to prevent and cure inherited diseases was supported. Morality and religion have great influence on the attitude of Nigerians towards genome modification, but the influence of religion and morality is not unequivocal. Multiple regression analysis of Nigerian public responses shows that gender (females), age (19–30 years), monthly income (NGN 0 to 30,000), and level of education (tertiary) are significantly associated with approval of human genome editing, but the survey of health workers and bio-scientists shows no significant association except for females who approve and Muslims who disapprove of human genome editing.
... Taking the case of choosing between two embryos as an example, if one is expected to have a life with a net negative state of welfare (e.g. having Tay-Sachs disease), it can be argued that we have a moral obligation to not 4 The reader can find some valuable discussions on the topic elsewhere (Ishii, 2017;Coller, 2019;Gabel and Moreno, 2019). 5 In nonhuman animals, this inherent nature is often referred to as telos, which does not always entail a fixist viewpoint on species. ...
Animal breeding is a mainstay of our relationship with domesticated species. However, it is sometimes leading to serious health and welfare issues, such as canine brachycephaly or double-muscling phenotype in Belgian Blue cattle. How then can we re-think our breeding system in animals? In this paper, I discuss the ethics of domestic animal breeding and new ways to achieve it. In doing so, I focus primarily on the concept of eugenics and its two major accounts: authoritarian and liberal eugenics. Indeed, the debates surrounding eugenics in humans is a quite prolific framework to question how we can justify animal breeding and has the merits to clarify the conditions needed to consider some practices as morally wrong ( e.g. in the case of authoritarian eugenics). I argue that pure-bred breeding is comparable in many ways with authoritarian eugenics primarily because it does not consider the benefits for the animals but external factors such as beauty, productivity or certain behaviors. But arguing so raises the question whether this renders all types of animal breeding unethical. I refute this conclusion and give some arguments to support an active use of more ethical kinds of breeding systems. Specifically, I explore the concept of liberal eugenics and its limitations to defend a breeding practice that is both liberal and responsible. Such new standards can warrant a focus on animal welfare and put forward the central role of breeders in this process.
... Las preocupaciones en materia de bioética más discutidas en debates internacionales, convenios y moratorias son las siguientes: la falta de autonomía de las generaciones futuras para decidir/consentir respecto de las modificaciones a su ADN; el que los científicos cambien el curso de la vida y la naturaleza humana, es decir que jueguen a ser dios; las presiones que la edición podría generar para los padres, sobre todo cuando se trata de proyectos de mejoramiento humano, es decir, modificar el ADN para crear niños más inteligentes, altos o con cierto talento especial. En este mismo sentido, se debate sobre los niños diseñados y los problemas sociales (desigualdad) que la edición podría generar, ya que no todos podrían tener acceso a las nuevas tecnologías (Ormond et al., 2017;Coller, 2019). Preocupa además, que la edición abra la puerta a nuevas formas de eugenesia (Comfort, 2018) y la potencial aplicación de la edición con fines criminales y terroristas (Lewis, 2016). ...
El artículo explora la genómica y sus ideas biologizantes sobre la raza. Problematiza las nociones de “elección” y “autonomía” que suelen respaldar argumentos a favor de la edición hereditaria del genoma humano. Se advierte sobre los riesgos de una eugenesia neoliberal que reproduzca, desde los individuos y ya no desde el estado, conocidas jerarquías raciales. Se discuten las implicaciones de la reiteración de la raza como una realidad biológica. El artículo argumenta que las nuevas ciencias de la vida plantean retos que afectan especialmente a las mujeres y a las poblaciones racializadas negativamente. Sin un marco legislativo adecuado, estas tecnologías podrían abrir la puerta a un nuevo proyecto eugenésico con un poder sin precedentes.
... D isruptive genome editing technologies, such as CRISPR-Cas9, are developing at a rapid pace and lead to ethical and societal questions which cannot be answered by considering only pragmatic arguments such as safety and efficacy (Almeida and Ranisch, 2022;Coller, 2019;Kleiderman and Ogbogu, 2019;Smith et al., 2012). Many ethical concerns arising from values and social, cultural and religious beliefs cannot be addressed by scientists alone, especially when it comes to heritable genome editing (HGE) (WHO, 2021). ...
Human genome editing technologies are advancing at a rapid pace, and their potential disruptive implications lead to ethical and societal questions that cannot be addressed by scientists alone. Further consideration of different stakeholders’ views on human genome editing is crucial to translate society’s needs and values into thoughtful regulations and policies. We therefore explored the views of carriers of autosomal dominant disorders on somatic and heritable genome editing (SGE and HGE) and the role of their (secular or religious) worldviews. This group of stakeholders would be most impacted by the eventual clinical application of genome editing technologies and therefore their views must be taken into account. Ten in-depth semi-structured interviews were conducted, and data were analysed using reflexive thematic analysis. We found an overarching theme: ‘Balancing between the desire to prevent serious diseases in individuals through HGE, and the fear of the harmful impact on society and nature’ and three main themes: ‘The benefits of SGE and HGE for individuals’, ‘the societal consequences of using HGE’, and ‘the consequences of interfering with nature through HGE’. Although the lived experiences of the participants varied, they were positive towards the safe use of SGE regardless of the severity of conditions, and most participants were positive towards the use of HGE but only to prevent severe genetic conditions. A few participants were against using HGE in any case, regardless of the severity of a condition, based on their religious beliefs. However, most participants with either religious or secular worldviews reported similar views on HGE, both regarding their desire to prevent serious genetic disorders and their fear of the impact on society and nature if HGE were implemented more widely. Reflecting on HGE involved complex and often ambivalent views. When engaging different stakeholders, space is needed for ambivalence and the weighing of values.
... Las preocupaciones en materia de bioética más discutidas en debates internacionales, convenios y moratorias son las siguientes: la falta de autonomía de las generaciones futuras para decidir/consentir respecto de las modificaciones a su ADN; el que los científicos cambien el curso de la vida y la naturaleza humana, es decir que jueguen a ser dios; las presiones que la edición podría generar para los padres, sobre todo cuando se trata de proyectos de mejoramiento humano, es decir, modificar el ADN para crear niños más inteligentes, altos o con cierto talento especial. En este mismo sentido, se debate sobre los niños diseñados y los problemas sociales (desigualdad) que la edición podría generar, ya que no todos podrían tener acceso a las nuevas tecnologías (Ormond et al., 2017;Coller, 2019). Preocupa además, que la edición abra la puerta a nuevas formas de eugenesia (Comfort, 2018) y la potencial aplicación de la edición con fines criminales y terroristas (Lewis, 2016). ...
El artículo explora la genómica y sus ideas biologizantes sobre la raza. Problematiza las nociones de “elección” y “autonomía” que suelen respaldar argumentos a favor de la edición hereditaria del genoma humano. Se advierte sobre los riesgos de una eugenesia neoliberal que reproduzca, desde los individuos y ya no desde el estado, conocidas jerarquías raciales. Se discuten las implicaciones de la reiteración de la raza como una realidad biológica. El artículo argumenta que las nuevas ciencias de la vida plantean retos que afectan especialmente a las mujeres y a las poblaciones racializadas negativamente. Sin un marco legislativo adecuado, estas tecnologías podrían abrir la puerta a un nuevo proyecto eugenésico con un poder sin precedentes.
... Despite the promise of CRISPR and other genome editing technologies, it is widely recognised that they raise large ethical and policy questions (Yotova, 2017;Getz et al., 2020;Eissenberg, 2021;Evans, 2020;Evans, 2021;Coller, 2019;Bubela et al., 2017). In response, in 2020, the World Health Organisation (WHO) formed an expert panel, the WHO Expert Advisory Committee on Developing Global Standards for Governance and Oversight on Genome Editing (the 'WHO GE Committee'), to examine global responses to the increasing availability of genome editing. ...
Clustered regularly interspaced short palindromic repeats and other genome editing technologies have the potential to transform the lives of people affected by genetic disorders for the better. However, it is widely recognised that they also raise large ethical and policy questions. The focus of this article is on how national genome editing policy might be developed in ways that give proper recognition to these big questions. The article first considers some of the regulatory challenges involved in dealing these big ethical and social questions, and also economic issues. It then reviews the outcomes of a series of major reports on genome editing from international expert bodies, with a particular focus on the work of the World Health Organization’s expert committee on genome editing. The article then summarises five policy themes that have emerged from this review of the international reports together with a review of other literature, and the authors’ engagement with members of the Australian public and with a wide range of experts across multiple disciplines. Each theme is accompanied by one to three pointers for policymakers to consider in developing genome editing policy.
... Bu bağlamda, germ hattı modifikasyonu, genetik çeşitliliğin kaybolmasına neden olabileceği gibi mükemmel özelliklere sahip çocukların (tasarım bebekler) doğmasına da yol açabilecektir. Dolayısıyla yalnızca belirli bir sosyoekonomik sınıftan insanların elde edebileceği fiziksel ve zihinsel yeteneklerin, toplumdaki bazı bireylere haksız bir üstünlük kazandırma ihtimali endişe oluşturmaktadır (Coller, 2019). 2015 yılında, MIT Technology Review'de basılan "Mükemmel Bebeği Tasarlamak" başlıklı makalede, Çin ve Birleşik Krallık'taki bilim adamlarının yanı sıra ABD'deki üç araştırma merkezinin insan germ hattı hücreleri ve embriyolarının modifikasyonu üzerinde çalıştığı açıklanmıştır (Regalado, 2015). ...
CRISPR-Cas teknolojisi, canlı bir organizmanın genomunu, endojen genlerin modifikasyonu veya eksojen genlerin entegrasyonu ile düzenleyen bir genetik mühendisliği tekniğidir. Bakterilerdeki adaptif bağışıklıktan sorumlu olan CRISPR-Cas sisteminin keşfi ve bir genom düzenleme aracına dönüştürülmesi genetik mühendisliği alanında devrim etkisi yapmıştır. CRISPR-Cas teknolojisini, önceki tekniklerden farklı kılan hemen her organizmanın genomuna kolaylıkla uygulanabilen hassas, verimli ve düşük maliyetli bir yöntem olmasıdır. Keşfinden günümüze kadar geçen süreçte tıp, biyomedikal, tarım ve hayvancılık gibi pekçok alanda kullanılabilecek umut verici bir araç olduğu kanıtlanmıştır. CRISPR-Cas teknolojisinin geniş uygulama potansiyeli, kolaylığı ve düşük maliyeti kötü niyetli veya sorumsuzca kullanılma olasılığını artırmaktadır. Bu teknolojinin negatif yönlü kullanım olasılığı ve yaşanabilecek teknik başarısızlıklar, başta germ hattı genom düzenlemeleri olmak üzere birçok alandaki uygulamalarıyla ilgili etik ve ahlaki kaygıları artırmış ve biyogüvenlik tartışmalarını gündeme getirmiştir. Bazı ülkelerde CRISPR-Cas ve diğer genom düzenleme tekniklerinin kullanımı ile ilgili politikalar bulunmakla birlikte birçok ülkede genom düzenlemelerini özel olarak ele alan yasal düzenlemeler hala geliştirilme aşamasında veya henüz bulunmamaktadır. Bu derlemede CRISPR-Cas teknolojisinin temel mekanizması açıklanmış, tıp, biyomedikal, tarım ve hayvancılıktaki uygulamalarına örnekler verilmiş ve potansiyel riskler ve yasal düzenlemeler üzerinde durulmuştur.
... Second, rigorous evaluations must be carried out on the issues of safety, tolerability, feasibility, and efficacy [80]. In this regard, some forms of therapeutic technologies leading to higher risks of genetic modifications of the human genome, such as the CRISPR-Cas9-mediated genomeediting approach, cannot meet basic safety and efficacy standards and have proven to be ethically unacceptable thus far, as reviewed and discussed by an international committee cosponsored by the US National Academy of Sciences and the National Academy of Medicine [81]. Moreover, phenotypic toxicity and undesired "off-target" effects are recurrent questions producing potential risks and adverse effects in many novel therapeutic choices for IDs, such as virus-mediated gene replacement therapy, pharmacological small-molecule approaches, and epi-drugs, and the prevention of these risks and adverse effects must be emphasized in preclinical studies. ...
Genomic imprinting is an epigenetic phenomenon of monoallelic gene expression pattern depending on parental origin. In humans, congenital imprinting disruptions resulting from genetic or epigenetic mechanisms can cause a group of diseases known as genetic imprinting disorders (IDs). Genetic IDs involve several distinct syndromes sharing homologies in terms of genetic etiologies and phenotypic features. However, the molecular pathogenesis of genetic IDs is complex and remains largely uncharacterized, resulting in a lack of effective therapeutic approaches for patients. In this review, we begin with an overview of the genomic and epigenomic molecular basis of human genetic IDs. Notably, we address ethical aspects as a priority of employing emerging techniques for therapeutic applications in human IDs. With a particular focus, we delineate the current field of emerging therapeutics for genetic IDs. We briefly summarize novel symptomatic drugs and highlight the key milestones of new techniques and therapeutic programs as they stand today which can offer highly promising disease-modifying interventions for genetic IDs accompanied by various challenges.
... 4.13 Keeping in mind Sperry's remarks about free will -the experimental basis for which we will examine more closely later in this chapter -it is useful immediately to point out that the materialistbehaviorist conception of the human brain as a mechanism something like a clock, or in today's transhumanism, a computer (Bostrom, 2005;Coller, 2019;Marchant, 2021;, has encouraged clinicians and doctors dealing with human infants to regard them as incapable of volitional actions. Sperry's research showed that materialist-behaviorist doctrine to be mistaken. ...
The human language capacity stands at the very top of the intellectual abilities of us human beings, and it ranks incommensurably higher than the intellectual powers of any other organism or any robot. It vastly exceeds the touted capacities of "artificial intelligence" with respect to creativity, freedom of will (control of thoughts and words), and moral responsibility. These are traits that robots cannot possess and that can only be understood by human beings. They are no part of the worlds of robots and artificial intelligences, but those entities, and all imaginable fictions, etc., are part of our real world...
True narrative representations (TNRs) can express and can faithfully interpret every kind of meaning or form in fictions, errors, lies, or nonsensical strings seeming in any way to be representations. None of the latter, however, can represent even the simplest TNR ever created by an intelligent person. It has been proved logically, in the strictest forms of mathematical logic, that all TNRs that seem to have been produced by mechanisms, robots, or artificial intelligence, must be contained within a larger and much more far-reaching TNR that cannot be explained mechanistically by any stretch of imagination. These unique constructions of real intelligence, that is, genuine TNRs, (1) have the power to determine actual facts; (2) are connected to each other in non-contradictory ways, and (3) are generalizable to all contexts of experience to the extent of the similarities of those contexts up to a limit of complete identity. What the logicomathematical theory of TNRs has proved to a fare-thee-well is that only TNRs have the three logical properties just iterated. No fictions, errors, lies, or any string of nonsense has any of those unique formal perfections.
The book is about how the human language capacity is developed over time by human beings beginning with TNRs known to us implicitly and actually even before we are born. All scientific endeavors, all the creations of the sciences, arts, and humanities, all the religions of the world, and all the discoveries of experience utterly depend on the prior existence of the human language capacity and our power to comprehend and produce TNRs. Without it we could not enjoy any of the fruits of human experience. Nor could we appreciate how things go wrong when less perfect representations are mistaken, whether accidentally or on purpose, for TNRs.
In biology, when DNA, RNA, and protein languages are corrupted, the proximate outcome is disorder, followed by disease if not corrected, and, in the catastrophic systems failures known as death in the long run. The book is about life and death. Both are dependent on TNRs in what comes out to be an absolute dependency from the logicomathematical perspective. Corrupt the TNRs on which life depends, and death will follow. Retain and respect TNRs and life can be preserved. However, ultimate truth does not reside in material entities or the facts represented by TNRs. It resides exclusively in the TNRs themselves and they do not originate from material entities. They are from God Almighty and do not depend at all on any material thing or body. TNRs outrank the material facts they incorporate and represent. It may seem strange, but the result is more certain, I believe, than the most recent findings of quantum physics. Representations are connected instantaneously. Symbol speed is infinitely faster than the speed of light.
In the larger perspective of history, when TNRs are deliberately corrupted, the chaos of wars, pestilence, and destruction follows as surely as night follows day. The human language capacity makes us responsible in a unique manner for our thoughts, words, and actions. While it is true that no one ever asked us if we wanted to have free will or not, the fact that we have it can be disputed only by individuals who engage in a form of self-deception that borders on pathological lying, the kind that results when the deceiver can no longer distinguish between the actions he or she actually performed in his or her past experience and the sequences of events that he or she invented to avoid taking responsibility for those events, or to take credit for actions he or she never performed. On the global scale such misrepresentations lead to the sort of destruction witnessed at Sodom in the day of Abraham. That historical destruction has recently been scientifically revealed at the site of Tall el-Hammam in Jordan. More about that and all of the foregoing in the book.
If you encounter errors, please point them out to the author at joller@bellsouth.net. Thank you.
... touches on the very nature of life, triggering intense public scrutiny, especially when framed as decisions about "designer babies" (Coller 2019). The examples are plentiful, but the conclusion always points to the public impact of technology. ...
Innovation is a powerful and complex social discourse with tremendous social, political, and philosophical implications. This article describes the methodological characteristics of an educational activity promoting critical discussions about the meaning of innovation with engineering students. This activity, called the Meaning of Innovation Dialogue (MID), is based on argumentation methods and seeks to structure speech to facilitate inclusive, supported, and controversial dialogue. It is structured in two phases: (a) critical case analysis through conversations about science, technology, and societal readings, exploring contemporary cases of technological innovation; (b) a Socratic conversation about the meaning of innovation, defined in three guiding questions: What is innovation (descriptive and prescriptive analysis)? What should be the purpose of innovation (deontological, teleological, and axiological analysis)? How should innovation be governed (policy and democratic analysis)? This activity seeks to structure the forms of conversation but keep its content open to students’ subjective experiences and sociocultural contexts. Ultimately, this activity is based on the need to have engineering students talk about technological-societal co-construction broadly, beyond evidenced cases of technological failure or unethical behaviors.
... touches on the very nature of life, triggering intense public scrutiny, especially when framed as decisions about "designer babies" (Coller 2019). The examples are plentiful, but the conclusion always points to the public impact of technology. ...
This manuscript appraises an early introduction to basic cryptography through a specific educational experience for engineering students, namely, replicating the ENIGMA cipher machine (García-Martínez et al. in J Interact Des Manufact (IJIDeM), 1–18, 2021). Using an action research approach, we designed a didactic sequence with 20 activities focused on strengthening the students’ programming skills. This teaching intervention introduced LabVIEW as a visual tool that promotes the correct programming of the ENIGMA code. In turn, we verified that the students developed metacognitive skills of autonomy and self-regulation and computational thinking competencies in this study. Thus, the intervention was student-centered, and the teacher had a decentralized role.
... These are programmable site-specific nucleases that have shown therapeutic potential; however, the applications of these technologies are still being perfected. Although CRISPR/CRISPR associated protein 9 (Cas9) systems are reported to have shown superiority over transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases (ZFNs) on certain aspects, effects of off-target mutations remain untackled and several ethical questions remain unanswered (7,10). ...
... touches on the very nature of life, triggering intense public scrutiny, especially when framed as decisions about "designer babies" (Coller 2019). The examples are plentiful, but the conclusion always points to the public impact of technology. ...
This book contains peer-reviewed selected papers of the 7th International Conference on Educational Innovation (CIIE 2020). It presents excellent educational practices and technologies complemented by various innovative approaches that enhance educational outcomes. In line with the Sustainable Development Goal 4 of UNESCO in the 2030 agenda, CIIE 2020 has attempted to “ensure inclusive and equitable quality education and promote lifelong learning opportunities for all.” The CIIE 2020 proceeding offers diverse dissemination of innovations, knowledge, and lessons learned to familiarize readership with new pedagogical-oriented, technology-driven educational strategies along with their applications to emphasize their impact on a large spectrum of stakeholders including students, teachers and professors, administrators, policymakers, entrepreneurs, governments, international organizations, and NGOs.
... To analyse some implications of allowing heritable genome editing interventions in humans, it is relevant to explore underlying values and associated ethical considerations. Building on previous work by other authors (e.g., Coller, 2019;de Wert et al., 2018;van Dijke et al., 2018;Mulvihill et al., 2017;Ishii, 2015), this article aims to provide context to the debates taking place and critically analyse some of the major pragmatic, categorical and sociopolitical considerations raised to date in relation to human heritable genome editing. Specifically, we explore some key categorical and sociopolitical considerations to underline some of the possible barriers to societal acceptance, key outstanding questions requiring consideration, and possible implications at the individual and collective level. ...
Genetic engineering has provided humans the ability to transform organisms by direct manipulation of genomes within a broad range of applications including agriculture (e.g., GM crops), and the pharmaceutical industry (e.g., insulin production). Developments within the last 10 years have produced new tools for genome editing (e.g., CRISPR/Cas9) that can achieve much greater precision than previous forms of genetic engineering. Moreover, these tools could offer the potential for interventions on humans and for both clinical and non-clinical purposes, resulting in a broad scope of applicability. However, their promising abilities and potential uses (including their applicability in humans for either somatic or heritable genome editing interventions) greatly increase their potential societal impacts and, as such, have brought an urgency to ethical and regulatory discussions about the application of such technology in our society. In this article, we explore different arguments (pragmatic, sociopolitical and categorical) that have been made in support of or in opposition to the new technologies of genome editing and their impact on the debate of the permissibility or otherwise of human heritable genome editing interventions in the future. For this purpose, reference is made to discussions on genetic engineering that have taken place in the field of bioethics since the 1980s. Our analysis shows that the dominance of categorical arguments has been reversed in favour of pragmatic arguments such as safety concerns. However, when it comes to involving the public in ethical discourse, we consider it crucial widening the debate beyond such pragmatic considerations. In this article, we explore some of the key categorical as well sociopolitical considerations raised by the potential uses of heritable genome editing interventions, as these considerations underline many of the societal concerns and values crucial for public engagement. We also highlight how pragmatic considerations, despite their increasing importance in the work of recent authoritative sources, are unlikely to be the result of progress on outstanding categorical issues, but rather reflect the limited progress on these aspects and/or pressures in regulating the use of the technology.
... Driven by technology development, updates to the genetic firmware, e.g., via gene editing, will inevitably be considered and attempts will be likely made. A recent report on the human genome editing "supports crossing what has been a bright red line by recommending that clinical trials of heritable human genome editing be allowed" to prevent "a serious disease or condition" [180]. Without doubt, psychiatric disorders, including addiction, are "serious" despite their fuzzy diagnostic thresholds. ...
Defining the traits and phenotypes as well as their adequate measurement is critically important for genetic research. This chapter reviews the nature of the traits pertaining to substance use, the variety of related phenotypic definitions, and their influence on research and practice. The binary view on the extreme forms of substance use, commonly conceived of as a psychiatric disorder, addiction (substance use disorder), is juxtaposed with the alternative perspective of liability to disorder. This complex behavioral trait, with its numerous phenotypic manifestations related to the variety of psychoactive substances, is also shown to have a substantial non-substance-specific, common (general) liability component, underlying co-occurrence and changes in the use of different substances. The liability perspective allows reversal of the traditional focus of biomedical research on risk/disease to the resistance/health aspect of liability. The measurement of this trait is discussed, along with the analysis of disorder symptoms as its indicators. The role of genetic studies in understanding substance use, with their prospects and limitations, is reviewed.KeywordsAddictionRiskResistanceGeneticsCommon liabilityComplex disorders
... With the development of medical and biological technology and the adoption of these technologies in healthcare, especially in special departments, the scope of traditional NI control can no longer meet the needs of biosafety management in military central hospitals. Some technologies, such as those involved in synthetic biology, gene therapy, and stem cell therapy, have been adopted by hospitals, which have significant biosafety concerns (including ethical concerns) for both the patient and environment in the case of their misuse (Coller, 2019;Memi et al., 2018;Volarevic et al., 2018;Wang & Zhang, 2019). For example, when genetic technology is used in reproductive medicine, it may threaten human health and cause serious medical ethical crises (Wang & Yang, 2019). ...
To establish biosafety risk-management guidelines for clinical departments of military central hospitals in China. Using failure mode and effects analysis (FMEA), we assessed the biosafety risk priority number (RPN) of clinical departments of three military central hospitals. Nosocomial infection (NI), medical substance-associated accident (MSA), medical technology misuse (MTM), and synthetic RPN were 0.50 to 4.37, 0.50 to 2.91, 0.50 to 3.42, and 0.64 to 3.28, respectively. NI prevention investment was negatively correlated with NI risk, while NI RPN was positively correlated with MSA RPN. There were significant differences between groups of departments in synthetic and MTM RPN. NI, MSA, and MTM constitute a hospital biosafety risk. However, their risk factors are distributed differently among departments. Traditional NI prevention investment can reduce NI risk, but such investments were not effective for MSA and MTM. Targeted measures need to be taken by referring to RPN and risk levels derived from FMEA.
... The risks of somatic gene-editing are highly outweighed its benefit in treatment and long-term efficacy. A few risks needs taking into consideration in germline geneediting: (1) any insertion/indels mutation in germline cells can cause unpredictable changes in next generation; (2) the informed consent from the next generation is impossible to be obtained (10). In fact, for most monogenic diseases, assisted reproductive technology (ART) utilizing in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD) is capable enough to avoid the bequeathal of disease (11). ...
In recent years, the vital role of genetic factors in human diseases have been widely recognized by scholars with the deepening of life science research, accompanied by the rapid development of gene-editing technology. In early years, scientists used homologous recombination technology to establish gene knock-out and gene knock-in animal models, and then appeared the second-generation gene-editing technology zinc-finger nucleases (ZFNs) and transcription activator–like effector nucleases (TALENs) that relied on nucleic acid binding proteins and endonucleases and the third-generation gene-editing technology that functioned through protein–nucleic acids complexes—CRISPR/Cas9 system. This holds another promise for refractory diseases and genetic diseases. Cardiovascular disease (CVD) has always been the focus of clinical and basic research because of its high incidence and high disability rate, which seriously affects the long-term survival and quality of life of patients. Because some inherited cardiovascular diseases do not respond well to drug and surgical treatment, researchers are trying to use rapidly developing genetic techniques to develop initial attempts. However, significant obstacles to clinical application of gene therapy still exists, such as insufficient understanding of the nature of cardiovascular disease, limitations of genetic technology, or ethical concerns. This review mainly introduces the types and mechanisms of gene-editing techniques, ethical concerns of gene therapy, the application of gene therapy in atherosclerosis and inheritable cardiovascular diseases, in-stent restenosis, and delivering systems.
... It is recommended that experimental germline genome editing scenarios can proceed if: a) it is restricted to preventing transmission of a serious disease or condition, b) the edit is a modification to a common DNA sequence known not to be as-sociated with disease, and c) the research is conducted under a stringent set of ethical and regulatory require-ments. Crossing the red line of germline genome editing raises important bio-ethical issues, most serious concern about the potential negative impact on individuals with disabilities [68]. ...
... However, the development of gene therapy is not always smooth sailing. From the death of the subject due to the fatal immune response in a clinical trial of adenovirus gene therapy conducted by Dr. James Wilson of the University of Pennsylvania in 1999 to the gene-editing babies event in 2018, gene therapy always arouses widespread discussion and controversy internationally, especially for the ethics of editing the human genome [83][84][85]. These challenges and opportunities inspire researchers to go in new directions and drive development of gene therapy for human health. ...
Alzheimer’s disease is a progressive neurodegenerative disorder characterized by extracellular amyloid beta peptides and neurofibrillary tangles consisted of intracellular hyperphosphorylated Tau in the hippocampus and cerebral cortex. Most of the mutations in key genes that code for amyloid precursor protein can lead to significant accumulation of these peptides in the brain and cause Alzheimer’s disease. Moreover, some point mutations in amyloid precursor protein can cause familial Alzheimer’s disease, such as Swedish mutation (KM670/671NL) and A673V mutation. However, recent studies have found that the A673T mutation in amyloid precursor protein gene can protect against Alzheimer’s disease, even if it is located next to the Swedish mutation (KM670/671NL) and at the same site as A673V mutation, which are pathogenic. It makes us curious about the protective A673T mutation. Here, we summarize the most recent insights of A673T mutation, focus on their roles in protective mechanisms against Alzheimer’s disease, and discuss their involvement in future treatment.
... Since ex vivo culture of blood cells is similar to in vitro cell culture, and gene transmission to blood cells is simpler than delivery to solid tissues, this technique has been tested in particular in blood cells. Hematopoietic stem cells (HSCs) are harvested from a patient, modified, and then re-engrafted to the patient of origin because HSCs can live outside of the body and return to the bone marrow following transplantation in ex vivo editing therapy of blood cells [1,55]. Clinical trials of therapeutic genome editing using CRISPR/Cas9 tools are currently in phase I for a few diseases. ...
CRISPR/Cas9 systems, in particular, have emerged as an important and promising technology for in vitro and in vivo genomic manipulation. Although genome editing has been used in the cardiovascular community as a scientific tool to study disease pathogenesis, therapeutic genome editing has yet to be used in clinical practice. PCSK9 is one of the most promising therapeutic genome editing candidates in the liver, and it has been thoroughly studied for cardiovascular disease risk reduction. Despite this, owing to the inefficiency of current genome editing technologies and distribution systems in the heart, treating the heart remains challenging. We should expect a steady stream of new editing approaches targeting wider use, given that clinical genome editing is still in its early stages but is rapidly progressing. It would be necessary to develop safe and reliable distribution systems in order to use such creative approaches in clinical settings.
... • Difficult to determine the timing of intervention. • Risk of unintended germline editing (59). ...
Hereditary or developmental neurological disorders (HNDs or DNDs) affect the quality of life and contribute to the high mortality rates among neonates. Most HNDs are incurable, and the search for new and effective treatments is hampered by challenges peculiar to the human brain, which is guarded by the near-impervious blood-brain barrier. Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR), a gene-editing tool repurposed from bacterial defense systems against viruses, has been touted by some as a panacea for genetic diseases. CRISPR has expedited the research into HNDs, enabling the generation of in vitro and in vivo models to simulate the changes in human physiology caused by genetic variation. In this review, we describe the basic principles and workings of CRISPR and the modifications that have been made to broaden its applications. Then, we review important CRISPR-based studies that have opened new doors to the treatment of HNDs such as fragile X syndrome and Down syndrome. We also discuss how CRISPR can be used to generate research models to examine the effects of genetic variation and caffeine therapy on the developing brain. Several drawbacks of CRISPR may preclude its use at the clinics, particularly the vulnerability of neuronal cells to the adverse effect of gene editing, and the inefficiency of CRISPR delivery into the brain. In concluding the review, we offer some suggestions for enhancing the gene-editing efficacy of CRISPR and how it may be morphed into safe and effective therapy for HNDs and other brain disorders.
... However, the development of gene therapy is not always smooth sailing. From the death of the subject due to the fatal immune response in a clinical trial of adenovirus gene therapy conducted by Dr. James Wilson of the University of Pennsylvania in 1999 to the gene-editing babies event in 2018, gene therapy always arouses widespread discussion and controversy internationally, especially for the ethics of editing the human genome [80][81][82]. These challenges and opportunities inspire researchers to go in new directions, and drive development of gene therapy for human health. ...
Alzheimer's Disease is a progressive neurodegenerative disorder characterized by extracellular amyloid beta peptides, and neurofibrillary tangles consisted of intracellular hyperphosphorylated Tau in the hippocampus and cerebral cortex. Most of the mutations in key genes that code for amyloid precursor protein can lead to significant accumulation of these peptides in the brain and cause Alzheimer's Disease. Moreover, Some point mutations in amyloid precursor protein can cause familial Alzheimer's Disease, such as Swedish mutation and A673V mutation. However, recent studies have found that the A673T mutation in amyloid precursor protein gene can protect against Alzheimer's Disease, even it is located next to the Swedish mutation and at the same site as A673V mutation, which are pathogenic. It makes us curious about the protective A673T mutation. Here, we summarize the most recent insights of A673T mutation, focus on their roles in protective mechanisms against Alzheimer's Disease, and discuss their involvement in future treatment.
The rapid evolution of gene editing technology has markedly improved the outlook for treating genetic diseases. Base editing, recognized as an exceptionally precise genetic modification tool, is emerging as a focus in the realm of genetic disease therapy. We provide a comprehensive overview of the fundamental principles and delivery methods of cytosine base editors (CBE), adenine base editors (ABE), and RNA base editors, with a particular focus on their applications and recent research advances in the treatment of genetic diseases. We have also explored the potential challenges faced by base editing technology in treatment, including aspects such as targeting specificity, safety, and efficacy, and have enumerated a series of possible solutions to propel the clinical translation of base editing technology. In conclusion, this article not only underscores the present state of base editing technology but also envisions its tremendous potential in the future, providing a novel perspective on the treatment of genetic diseases. It underscores the vast potential of base editing technology in the realm of genetic medicine, providing support for the progression of gene medicine and the development of innovative approaches to genetic disease therapy.
In this article, I explore the ethical dimensions of same-sex reproduction achieved through epigenome editing—an innovative and transformative technique. For the first time, I analyse the potential normativity of this disruptive approach for reproductive purposes, focusing on its implications for lesbian couples seeking genetically related offspring. Epigenome editing offers a compelling solution to the complex ethical challenges posed by traditional gene editing, as it sidesteps genome modifications and potential long-term genetic consequences. The focus of this article is to systematically analyse the bioethical issues related to the use of epigenome editing for same-sex reproduction. I critically assess the ethical acceptability of epigenome editing with reproductive purposes from multiple angles, considering harm perspectives, the comparison of ethical issues related to gene and epigenome editing, and feminist theories. This analysis reveals that epigenome editing emerges as an ethically acceptable means for lesbian couples to have genetically related children. Moreover, the experiments of a reproductive use of epigenome editing discussed in this article transcend bioethics, shedding light on the broader societal implications of same-sex reproduction. It challenges established notions of biological reproduction and prompts a reevaluation of how we define the human embryo, while poses some issues in the context of gender self-identification and family structures. In a world that increasingly values inclusivity and diversity, this article aims to reveal a progressive pathway for reproductive medicine and bioethics, as well as underscores the need for further philosophical research in this emerging and fertile domain.
Rett syndrome (RTT) is a rare but dreadful X-linked genetic disease that mainly affects young girls. It is a neurological disease that affects nerve cell development and function, resulting in severe motor and intellectual disabilities. To date, no cure is available for treating this disease. In 90% of the cases, RTT is caused by a mutation in methyl-CpG-binding protein 2 (MECP2), a transcription factor involved in the repression and activation of transcription. MECP2 is known to regulate several target genes and is involved in different physiological functions. Mouse models exhibit a broad range of phenotypes in recapitulating human RTT symptoms; however, understanding the disease mechanisms remains incomplete, and many potential RTT treatments developed in mouse models have not shown translational effectiveness in human trials. Recent data hint that the zebrafish model emulates similar disrupted neurological functions following mutation of the mecp2 gene. This suggests that zebrafish can be used to understand the onset and progression of RTT pathophysiology and develop a possible cure. In this review, we elaborate on the molecular basis of RTT pathophysi-ology in humans and model organisms, including rodents and zebrafish, focusing on the zebrafish model to understand the molecular pathophysiology and the development of therapeutic strategies for RTT. Finally, we propose a rational treatment strategy , including antisense oligonucleotides, small interfering RNA technology and induced pluripotent stem cell-derived cell therapy.
The reality of interacting genes and proteins is vastly complex and intricate with many unknowns which currently prevent us from solving the anti-ageing equation in terms of gene expression. Molecular studies involving genome modification should take into consideration the importance of apparently opposing genes and proteins which when seen as a whole, can orchestrate an optimal systemic balance. Gene expression is often a double-edged sword with positive effects turning negative when a particular gene is overexpressed. For this reason, the US National Academy of Sciences and the National Academy of Medicine have placed stringent restrictions on the promising genome editing methods to be used only for the specific DNA sequence associated with a transmissible genetic disease. Rejuvenation as a result of gene expression is still an open area of research with studies that have either been limited to in vitro research or clinical studies claiming success based on a limited perspective that selectively emphasises the benefits of certain genes while leaving the negative outcomes in the shadows of their silence. For example, some investigators relate the presence of ZMPSTE24, IGF1R, NGF4, EEF2, EIF4FBP1 CCL18, and other genes with “rejuvenation,” selectively focusing on potential benefits while ignoring the involvement of some of these genes in malignancies and inflammation. Well-controlled gene expression molecular experimental studies with mechanotherapy and effortless exercise have limited themselves to the observation of increased slow skeletal genes associated with muscle growth that do not present any adverse side effects. Overall, exercise and nutrition are still the safest and most ethical methods of gene expression at least until genome editing can be extended to delaying ageing, in the near or distant future. As observed in the research analysing gene expression as the result of different types of exercise, inflammatory events are counterbalanced by antagonizing anti-inflammatory ones. This signifies optimal biological homeostasis because health depends on the harmonious interaction of opposite processes levelling and stabilizing each other. Exercise modalities and lifestyle are still representing the cornerstone of delaying ageing and the most riskless method of increasing longevity by triggering processes that balance each other.
Genome-wide association studies have led to the identification of robust statistical associations of genetic variants with numerous brain-related traits, including neurological and psychiatric conditions, and psychological and behavioral measures. These results may provide insight into the biology underlying these traits and may facilitate clinically useful predictions. However, these results also carry the risk of harm, including possible negative effects of inaccurate predictions, violations of privacy, stigma and genomic discrimination, raising serious ethical and legal implications. Here, we discuss ethical concerns surrounding the results of genome-wide association studies for individuals, society and researchers. Given the success of genome-wide association studies and the increasing availability of nonclinical genomic prediction technologies, better laws and guidelines are urgently needed to regulate the storage, processing and responsible use of genetic data. Also, researchers should be aware of possible misuse of their results, and we provide guidance to help avoid such negative impacts on individuals and society.
CRISPR (clustered regularly interspaced short palindromic repeats) is a Nobel Prize–winning technology that holds significant promise for revolutionizing the prevention and treatment of human disease through gene editing. However, CRISPR’s public health implications remain relatively uncertain and underdiscussed because (1) targeting genetic factors alone will have limited influence on population health, and (2) minority populations (racial/ethnic, sexual and gender)—who bear the nation’s greatest health burdens—historically suffer unequal benefits from emerging health care innovations and tools.
This article introduces CRISPR and its potential public health benefits (e.g., improving virus surveillance, curing genetic diseases that pose public health problems such as sickle cell anemia) while outlining several major ethical and practical threats to health equity. This includes minorities’ grave underrepresentation in genomics research, which may lead to less effective and accepted CRISPR tools and therapies for these groups, and their anticipated unequal access to these tools and therapies in health care.
Informed by the principles of fairness, justice, and equitable access, ensuring gene editing promotes rather than diminishes health equity will require the meaningful centering and engagement of minority patients and populations in gene-editing research using community-based participatory research approaches. (Am J Public Health. 2023;113(8):874–882. https://doi.org/10.2105/AJPH.2023.307315 )
Philosophers and neuroscientists address central issues in both fields, including morality, action, mental illness, consciousness, perception, and memory.
Philosophers and neuroscientists grapple with the same profound questions involving consciousness, perception, behavior, and moral judgment, but only recently have the two disciplines begun to work together. This volume offers fourteen original chapters that address these issues, each written by a team that includes at least one philosopher and one neuroscientist, who integrate disciplinary perspectives and reflect the latest research in both fields. Topics include morality, empathy, agency, the self, mental illness, neuroprediction, optogenetics, pain, vision, consciousness, memory, concepts, mind wandering, and the neural basis of psychological categories.
The chapters first address basic issues about our social and moral lives: how we decide to act and ought to act toward each other, how we understand each other's mental states and selves, and how we deal with pressing social problems regarding crime and mental or brain health. The following chapters consider basic issues about our mental lives: how we classify and recall what we experience, how we see and feel objects in the world, how we ponder plans and alternatives, and how our brains make us conscious and create specific mental states.
Contributors
Sara Abdulla, Eyal Aharoni, Corey H. Allen, Sara Aronowitz, Jenny Blumenthal-Barby, Ned Block, Allison J. Brager, Antonio Cataldo, Tony Cheng, Felipe De Brigard, Rachel N. Denison, Jim A. C. Everett, Gidon Felsen, Julia Haas, Hyemin Han, Zac Irving, Kristina Krasich, Enoch Lambert, Cristina Leon, Anna Leshinskaya, Jordan L. Livingston, Brian Maniscalco, Joshua May, Joseph McCaffrey, Jorge Morales, Samuel Murray, Thomas Nadelhoffer, Laura Niemi, Brian Odegaard, Hannah Read, Robyn Repko Waller, Sarah Robins, Jason Samaha, Walter Sinnott-Armstrong, Joshua August Skorburg, Shannon Spaulding, Arjen Stolk, Rita Svetlova, Natalia Washington, Clifford Workman, Jessey Wright
Mitochondrial replacement therapies (MRT) represent the most recent advancement in assisted reproductive technologies, allowing some women with mitochondrial diseases to birth—for the first time—babies without those diseases. MRT, however, are not without controversy: DNA is intentionally changed, and resulting babies have DNA from three people. Additionally, the change to DNA is considered germline therapy in some countries and is therefore banned. With MRT prohibited in some countries but commercially available in multiple other jurisdictions, policymakers and other key stakeholders are faced with questions about the legal and ethical challenges surrounding MRT and the rights and responsibilities of parents and donor mothers, MRT’s use to address broader problems of infertility, and issues surrounding the notions of family. This edited volume draws together leading experts from across the world and various disciplines to explore the novel legal, ethical, and policy questions posed by MRT, along with the broader societal and governance implications.
The article provides a brief overview of the history of gene therapy from its inception to the present. It describes the main events that characterize the periods of history of the formation of this therapeutic direction in medicine; the basis achievements and problems of each periods. It lists the main gene therapy drugs that licensed at different times listed; innovative gene therapy technologies, which are now use in clinical practice or are still at the stage of approbation. The article is a review of publications from the Scopus and PubMed and official information from public Internet sources.
Diyabetes mellitus (DM) pek çok sistemi etkileyen özellikle kardiyovasküler sistem üzerine olan etkisi ile mortalite ve morbiditeye sebep olan, vasküler hasar ve endotel fonksiyon bozukluğu ile seyreden bir karbonhidrat metabolizması bozukluğudur (1). Diyabetin sebep olduğu komplikasyonlar mikro ve makrovasküler komplikasyonlar olmak üzere ikiye ayrılır. Makrovasküler komplikasyonlar özellikle diyabetin sebep olduğu vasküler hasar ve inflamasyon nedeniyle oluşurken; aynı zamanda inme, miyokard infarktüsü, periferik arter hastalığı ve aterosklerotik kalp hastalığı gibi kardiyovasküler hastalıklar olarak karşımıza çıkmaktadır (2).
Mallory-Weiss yırtılması (MWT), yemek borusunun alt kısmında ve/veya midenin üst kısmında lineer, perforan olmayan mukozal laserasyon ile karakterizedir. Mallory ve Weiss, MWT'yi ilk kez 1929'da öğürme ve kusma şikayeti olan 15 alkolik hastada tanımladı(1). MWT, üst gastrointestinal sistem (GİS) kanamalarının %1-4 kadarından sorumludur. Kanama çoğu zaman, gastroözofageal bileşke noktasında mukozal veya submukozal laserasyonlardan kaynaklanır(2).
There is no question that genetic therapy has a potential to be the crowning achievement of modern medical science. There is a paradigm shift in clinical medicine for many genetic disorders that brings hope to irradicate the morbidity and mortality of many chronic conditions such as hemophilia. Although genetic diseases have been recognized for millennia, their underlying disease mechanisms and specific disease-gene link have only occurred in the last 50 years. For example, chromosomal conditions (e.g. trisomy 21) and contiguous gene deletion syndromes (e.g. 22q11.2 deletion syndrome) are more common and were earlier in their discovery, several single gene (monogenetic) conditions are clear better first targets for gene therapy. Hemophilia became one of the earliest candidates for gene therapy because of several desirable characteristics: (1) Although a rare disease, there are sufficient numbers of affected individuals (>20 k in the USA and >400 k worldwide). (2) Not only is hemophilia monogenetic, but both hemophilia A and B have an additional benefit of being X-linked and therefore only require one allele to be repaired (in men). (3) The therapeutic goals to prove that there is a clinically meaningful benefit that neither requires 100% factor level correction (mild diagnosis having levels at 5–40%) nor regulation of protein expression. (4) There are established clinical treatment standards and an excellent understanding of the disease process. (5) There are easy to measure outcomes to determine treatment effectiveness and success. (6) There is an existing network of infrastructure with plenty of experience and expertise at centers of excellence and hemophilia treatment centers. The excitement and buzz of yesterday’s imagination is rapidly translating into a growing number of clinical trials and hope for the development of tomorrow’s treatments. However, with almost every advancement in genetic therapy comes compounding societal skepticism and doubt surrounding the ethics of the newly coveted technology.KeywordsHemophiliaGeneticsInheritanceGene therapyGene transferGene editing
Notre recherche porte sur l’acceptabilité des biotechnologies médicales chez le grand public en France. Deux avancées médicales sont à l’étude : la thérapie génique et la xénotransplantation. Deux cent vingt-quatre personnes ont émis un jugement d’acceptabilité sur ces deux biotechnologies sur la base de scénarios élaborés selon la Théorie Fonctionnelle de la Cognition (Anderson, 1981, 1982, 1996). Dans l’étude sur la thérapie génique, les quatre facteurs sélectionnés – type de thérapie, probabilité d’apparition de la maladie, type de maladie, chances de succès de la thérapie – ont eu un impact significatif. Il apparaît sept manières différentes de juger de l’acceptabilité de la thérapie génique. Bien que les patterns de réponse diffèrent entre les clusters, le facteur Type de thérapie est le principal utilisé, permettant de discriminer les clusters. Près de 50% de nos participants sont favorables à la thérapie génique. Pour l’étude concernant la xénotransplantation, les trois facteurs ont un effet significatif sur le jugement d’acceptabilité. Néanmoins, seuls les facteurs Type de consentement et Urgence de l’intervention interviennent dans la formation des différents patterns de jugement des huit clusters. Près de 60% des participants tiennent compte principalement du consentement du patient et de sa famille. L’acceptabilité de ces biotechnologies médicales est bien influencée par les différents facteurs sélectionnés, permettant de dégager différents positionnements quant à ces questionnements éthiques.
The discipline of ‘public health genomics’ emerged as a need to provide ‘responsible and effective translation of genome-based knowledge and technologies for the benefit of the population’. It is becoming increasingly accepted that the one size fits all approach is going to be outdated soon. Targeted personalized medicines, therapies, and interventions approach will be the preferred form of treatment in the not too distant future. The fields of public health genomics, precision medicine, and precision public health have proven important aspects in improving population health. However, despite the advancements made, there are still improvements that need to be implemented to significantly improve health, especially within the developing countries. In this chapter we discuss the advancements made within the field and highlight challengers or future directions.
Human gene editing, particularly using the new CRISPR/Cas9 technology, will greatly increase the capability to make precise changes to human genomes. Human gene editing can be broken into four major categories: somatic therapy, heritable gene editing, genetic enhancement, and basic and applied research. Somatic therapy is generally well governed by national regulatory systems, so the need for global governance is less urgent. All nations are in agreement that heritable gene editing should not proceed at this time, but there is likely to be divergence if and when such procedures are shown to be safe and effective. Gene editing for enhancement purposes is not feasible today but is more controversial with the public, and many nations do not have well-developed regulatory systems for addressing genetic enhancement. Finally, different nations treat research with human embryos very differently based on deeply embedded social, cultural, ethical, and legal traditions. Several international governance mechanisms are currently in operation for human gene editing, and several other governance mechanisms have been proposed. It is unlikely that any single mechanism will alone be effective for governing human gene editing; rather, a polycentric or ecosystem approach that includes several overlapping and interacting components is likely to be necessary.
Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 22 is August 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
In the version of this article initially published online, four figure citations were incorrect on p.2: left-hand column, after “complex rearrangements,” “Supplementary Fig. 2a,b” should have been “Fig. 2a,b”; right-hand column, in three places, the citation for “Supplementary Fig. 3…” should have been for “Supplementary Fig. 2.” The errors have been corrected for the print, PDF and HTML versions of this article.
In discussions of the ethics of human gene therapy, it has become standard to draw a distinction between the use of human gene transfer techniques to treat health problems and their use to enhance or improve normal human traits. Some dispute the normative force of this distinction by arguing that it is undercut by the legitimate medical use of human gene transfer techniques to prevent disease-such as genetic engineering to bolster immune function, improve the efficiency of DNA repair, or add cellular receptors to capture and process cholesterol. If disease prevention is a proper goal of medicine, these critics argue, and the use of gene transfer techniques to enhance human health maintenance capacities will help achieve that goal, then the "treatment/enhancement" distinction cannot define the limits of legitimate gene therapy. In this paper, I argue that a line can be drawn between prevention and enhancement for gene therapy (and thus between properly medical and nonmedical uses of gene therapy), but only if one is willing to accept two rather old-fashioned claims: 1) Some health problems are best understood as if they were entities in their own right, reifiable as processes or parts in a biological system, with at least as much ontological objectivity and theoretical significance as the functions that they inhibit. 2) Legitimate preventive genetic health care should be limited to efforts to defend people from attack by these more robust pathological entities, rather than changing their bodies to evade social injustices.
Sheila Jasanoff and J. Benjamin Hurlbut call for an international network of scholars and organizations to support a new kind of conversation.
Transhumanism is a "technoprogressive" socio-political and intellectual movement that advocates for the use of technology in order to transform the human organism radically, with the ultimate goal of becoming "posthuman." To this end, transhumanists focus on and encourage the use of new and emerging technologies, such as genetic engineering and brain-machine interfaces. In support of their vision for humanity, and as a way of reassuring those "bioconservatives" who may balk at the radical nature of that vision, transhumanists claim common ground with a number of esteemed thinkers and traditions, from the ancient philosophy of Plato and Aristotle to the postmodern philosophy of Nietzsche. It is crucially important to give proper scholarly attention to transhumanism now, not only because of its recent and ongoing rise as a cultural and political force (and the concomitant potential ramifications for bioethical discourse and public policy), but because of the imminence of major breakthroughs in the kinds of technologies that transhumanism focuses on. Thus, the articles in this issue of The Journal of Medicine and Philosophy are either explicitly about transhumanism or are on topics, such as the ethics of germline engineering and criteria for personhood, that are directly relevant to the debate between transhumanists (and technoprogressives more broadly) and bioconservatives.