ABSTRACT
The Guidelines for Stem Cell Research and Clinical Translation, recently issued by the International Society for Stem Cell Research (ISSCR), include a number of substantive revisions. Significant changes include: (1) the bifurcation of 'Category 3 Prohibited research activities' in the 2016 Guidelines into 'Category 3A Research activities currently not permitted' and 'Category 3B Prohibited research activities' in the 2021 guidelines and (2) the move of heritable human genome editing research out of the 'prohibited' category and into the 'currently not permitted' category. These changes are noteworthy because of the absence of a clear demarcation line between the two categories insofar as, by definition, that which is 'prohibited' is 'currently not permitted', and vice versa. Permanence is not part of the definition of 'prohibition'. In principle, a prohibition can be rescinded at any time. This begs the question 'Why make a policy change that has no apparent practical effect?' One hypothesis is that the recategorisation of specific 'prohibited' research activities as 'currently not permitted' is meant to seed intuitions about which prohibited research activities should 'soon' be permitted subject to specialised scientific and ethics review and approval.
Subject(s)
Gene Editing , Stem Cell Research , Humans , Genome, HumanSubject(s)
Breast Feeding/psychology , COVID-19 Vaccines , Patient Selection , Pregnant Women/psychology , Research , Sexism , Adult , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/therapeutic use , Clinical Trials as Topic , Female , Health Services Accessibility , Humans , Pregnancy , Public HealthABSTRACT
Discussions and debates about the governance of human germline and heritable genome editing should be informed by a clear and accurate understanding of the global policy landscape. This policy survey of 106 countries yields significant new data. A large majority of countries (96 out of 106) surveyed have policy documents-legislation, regulations, guidelines, codes, and international treaties-relevant to the use of genome editing to modify early-stage human embryos, gametes, or their precursor cells. Most of these 96 countries do not have policies that specifically address the use of genetically modified in vitro embryos in laboratory research (germline genome editing); of those that do, 23 prohibit this research and 11 explicitly permit it. Seventy-five of the 96 countries prohibit the use of genetically modified in vitro embryos to initiate a pregnancy (heritable genome editing). Five of these 75 countries provide exceptions to their prohibitions. No country explicitly permits heritable human genome editing. These data contrast markedly with previously reported findings.
Subject(s)
CRISPR-Cas Systems , Embryo Research/legislation & jurisprudence , Gene Editing/legislation & jurisprudence , Genome, Human , Germ Cells , Embryonic Stem Cells , HumansABSTRACT
In September 2020, a detailed report on Heritable Human Genome Editing was published. The report offers a translational pathway for the limited approval of germline editing under limited circumstances and assuming various criteria have been met. In this perspective, some three dozen experts from the fields of genome editing, medicine, bioethics, law, and related fields offer their candid reactions to the National Academies/Royal Society report, highlighting areas of support, omissions, disagreements, and priorities moving forward.
Subject(s)
Gene Editing/ethics , Genome, Human , Human Experimentation/ethics , Academies and Institutes , Germ Cells , Humans , Research Report , SocietiesABSTRACT
As public interest advocates, policy experts, bioethicists, and scientists, we call for a course correction in public discussions about heritable human genome editing. Clarifying misrepresentations, centering societal consequences and concerns, and fostering public empowerment will support robust, global public engagement and meaningful deliberation about altering the genes of future generations.
Subject(s)
Gene Editing/ethics , Genome, Human/genetics , Bioethical Issues , Embryo, Mammalian , Germ Cells , HumansSubject(s)
Gene Editing/ethics , Gene Editing/legislation & jurisprudence , Germ-Line Mutation/genetics , Heredity/genetics , International Cooperation/legislation & jurisprudence , Embryo, Mammalian/metabolism , Female , Fertilization in Vitro , Gene Pool , Genetic Predisposition to Disease , Humans , Male , Morals , Ovum/metabolism , Risk Assessment , Social Change , Spermatozoa/metabolismABSTRACT
A new infrastructure is urgently needed at the global level to facilitate exchange on key issues concerning genome editing. We advocate the establishment of a global observatory to serve as a center for international, interdisciplinary, and cosmopolitan reflection. This article is the first of a two-part series.
Subject(s)
Bioethical Issues , Gene Editing/ethics , Gene Editing/legislation & jurisprudence , HumansABSTRACT
A new infrastructure is urgently needed at the global level to facilitate exchange on key issues concerning genome editing. We advocate the establishment of a global observatory to serve as a center for international, interdisciplinary, and cosmopolitan reflection. This article is the second of a two-part series.
Subject(s)
Gene Editing/ethics , Gene Editing/methods , Capacity Building , Global Health , HumansABSTRACT
Giulia Cavaliere and César Palacios-González argue that lesbian couples should have access to human nuclear genome transfer (so-called mitochondrial replacement) so that both members of the couple can have a genetic link to the child they intend to parent. Their argument is grounded in an appeal to reproductive freedom. In this Response, I address a number of concerns with their argument. These concerns relate to nomenclature, treating like cases alike, genetic-relatedness and the limits of reproductive rights. On this last point, I insist that we should not mistake 'wants' for 'needs' or 'rights'. I maintain that there is no right to biological parenthood, there is no compelling need for human nuclear genome transfer to satisfy a so-called need for genetically-related children, and we ought not to pander to an acquired desire (ie, want) for genetic filiation.
Subject(s)
Homosexuality, Female , Sexual and Gender Minorities , Child , Female , Freedom , Humans , Mitochondria , ParentsSubject(s)
CRISPR-Cas Systems , Gene Editing/methods , Genetic Therapy/methods , Human Genetics/ethics , Clinical Trials as Topic , Gene Editing/ethics , Gene Expression Regulation , Genetic Therapy/adverse effects , Humans , Neoplasms/genetics , Neoplasms/therapy , Translational Research, BiomedicalABSTRACT
A prospective first-in-human Phase 1 CRISPR gene editing trial in the United States for patients with melanoma, synovial sarcoma, and multiple myeloma offers hope that gene editing tools may usefully treat human disease. An overarching ethical challenge with first-in-human Phase 1 clinical trials, however, is knowing when it is ethically acceptable to initiate such trials on the basis of safety and efficacy data obtained from pre-clinical studies. If the pre-clinical studies that inform trial design are themselves poorly designed - as a result of which the quality of pre-clinical evidence is deficient - then the ethical requirement of scientific validity for clinical research may not be satisfied. In turn, this could mean that the Phase 1 clinical trial will be unsafe and that trial participants will be exposed to risk for no potential benefit. To assist sponsors, researchers, clinical investigators and reviewers in deciding when it is ethically acceptable to initiate first-in-human Phase 1 CRISPR gene editing clinical trials, structured processes have been developed to assess and minimize translational distance between pre-clinical and clinical research. These processes draw attention to various features of internal validity, construct validity, and external validity. As well, the credibility of supporting evidence is to be critically assessed with particular attention to optimism bias, financial conflicts of interest and publication bias. We critically examine the pre-clinical evidence used to justify the first-inhuman Phase 1 CRISPR gene editing cancer trial in the United States using these tools. We conclude that the proposed trial cannot satisfy the ethical requirement of scientific validity because the supporting pre-clinical evidence used to inform trial design is deficient.
Subject(s)
CRISPR-Cas Systems , Clinical Trials, Phase I as Topic/methods , Gene Editing/methods , Neoplasms/therapy , Research Design , Clinical Trials, Phase I as Topic/ethics , Humans , Melanoma/genetics , Melanoma/therapy , Multiple Myeloma/genetics , Multiple Myeloma/therapy , Neoplasms/genetics , Prospective Studies , Proto-Oncogenes/genetics , Reproducibility of Results , Sarcoma, Synovial/genetics , Sarcoma, Synovial/therapy , Translational Research, Biomedical/ethics , Translational Research, Biomedical/methods , United StatesSubject(s)
Gene Editing , Genome, Human , Clustered Regularly Interspaced Short Palindromic Repeats , Europe , Germ Cells , HumansABSTRACT
In this article, I argue that there is no compelling therapeutic 'need' for human nuclear genome transfer (so-called mitochondrial replacement) to prevent mitochondrial diseases caused by mtDNA mutations. At most there is a strong interest in (i.e. 'want' for) this technology on the part of some women and couples at risk of having children with mitochondrial disease, and perhaps also a 'want' on the part of some researchers who see the technology as a useful precedent - one that provides them with 'a quiet way station' in which to refine the micromanipulations techniques essential for other human germline interventions and human cloning. In advance of this argument, I review basic information about mitochondrial disease and novel genetic strategies to prevent the transmission of mutated mitochondria. Next, I address common features of contemporary debates and discussions about so-called mitochondrial replacement. First, I contest the cliché that science-and-(bio)technology is fast outpacing ethics. Second, I dispute the accuracy of the term 'mitochondrial replacement'. Third, I provide a sustained critique of the purported 'need' for genetically-related children. In closing, I call into question the mainly liberal defense of human nuclear genome transfer. I suggest an alternative frame of reference that pays particular attention to issues of social justice. I conclude that our limited resources (time, talent, human eggs, and money) should be carefully expended in pursuit of the common good, which does not include pandering to acquired desires (i.e., wants).