Heritable Human Genome Editing (2020) / Chapter Skim
Currently Skimming:
1 Introduction
1 Introduction
Pages 19-34
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From page 19... ...
But the use in humans of heritable genome editing raises many critical and potentially contentious issues. The challenge of assessing safety and efficacy is particularly great, since the effects may not be immediately apparent and could affect future generations.
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From page 20... ...
Eggs and sperm fuse during sexual reproduction to create a zygote, the initial single cell that continues the germline into the next generation. While heritable human ge nome editing would necessarily involve using editing reagents with germline cells or their precursors, not all such editing is intended to be inherited.
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From page 21... ...
However, the report went on to say that HHGE might be permissible sometime in the future, after much more research had been done on balancing risks and benefits, and identified 10 criteria for otential future clinical evaluation of the process as part of a p robust regulatory framework. Likewise, in a 2018 extension of its earlier report, the Nuffield Council on Bioethics stated that it could "envision circumstances in which heritable genome editing interventions should be permitted" (NCB, 2018, p.
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From page 22... ...
Despite what many had viewed as general agreement within scientific and clinical communities that it would be premature and irresponsible to undertake HHGE at this time, it had apparently taken place. In its concluding statement, the summit organizing committee described the reported clinical use of HHGE as "deeply disturbing" and criticized the violation of ethical standards and lack of transparency in the development, review, and conduct of the clinical procedures.
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From page 23... ...
. FORMATION OF THE INTERNATIONAL COMMISSION AND WORLD HEALTH ORGANIZATION EXPERT COMMITTEE Two international committees were convened following these calls to further develop an understanding of what would be involved in a responsible translational pathway toward HHGE and to make progress on effective coordination and governance of human genome editing.
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From page 24... ...
One in every 5,000 to 10,000 people develops a symptomatic mtDNA disease. In one method of MRT, referred to as maternal spindle transfer, eggs are harvested from the intended mother who has pathogenic mtDNA, and the chromosomes of the nuclear genome of each egg are removed and transferred to the donated eggs of a woman with healthy mtDNA from which the chromosomes of the nuclear genome have been removed.
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From page 25... ...
pronuclear transfer. For details, see Greenfield et al.
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From page 26... ...
MRT is only permitted for the prevention of serious mtDNA disease, with the additional caveats that licenses can only be granted to named clinics after demonstration of their competence, and any use is restricted to prospective parents with no suitable alternative for having an unaffected, genetically-related child. The steps involved in developing a translational pathway for MRT in the United Kingdom are summarized in Box 1-2.
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From page 27... ...
In parallel, the U.K.'s Nuffield Council on Bioethics conducted an inquiry into ethical issues raised by MRT. Based on the public dialogue and Nuffield Council report, the HFEA advised the Government that "there is general support for permitting mitochondrial replacement in the U.K., so long as it is safe enough to offer in a treatment setting and is done so within a regulatory framework" (HFEA, 2013, p.
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From page 28... ...
. Questions that deserve significant attention include how to effectively engage multiple sectors of the public, including genetic disease and disability communities, and how to incorporate the diverse input received into a country's decision-making processes.
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Beyond Commission's remit with any further clinical uses FIGURE 1-2 General elements that form a translational pathway for HHGE.
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5. Design appropriate protocols for obtaining consent from patients, for ob taining ethical approval from knowledgeable review committees, and for satisfying regulatory authorities.
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The outcomes of extensive societal deliberations and sufficient progress in preclinical development of the techniques for HHGE would together feed into a country's decision on whether or not HHGE could be considered for clinical use. If a country's legislative body does not permit the consideration of HHGE for the proposed purpose, the pathway toward clinical use cannot proceed beyond basic laboratory research and preclinical development.
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From page 32... ...
The Commission's deliberations included, among other activities, a public meeting held in August 2019, a request for public input to targeted questions gathered in September 2019, public webinars on genome editing technology held in October 2019, and a public workshop held in November 2019. At a third meeting in January 2020, Commission members developed the findings, conclusions, and recommendations presented in this report.
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From page 33... ...
Instead, the report describes the key elements that would need to form the foundation for a potential translational pathway for HHGE, lays out scientific and clinical issues that will need to be considered to undertake HHGE responsibly, and identifies preclinical and clinical requirements that would need to be met to establish safety and efficacy. ORGANIZATION OF THE REPORT This chapter introduces what the Commission means by a translational pathway toward possible future clinical uses of HHGE, should a country ever permit such use.
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From page 34... ...
The establishment of oversight mechanisms and infrastructure to govern the use of HHGE is critical to any responsible translational pathway and for preventing misuse of the technology.
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