Human Genome Editing Science, Ethics, and Governance (2017) / Chapter Skim
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5 Heritable Genome Editing
5 Heritable Genome Editing
Pages 111-136
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From page 111... ...
. "Heritable genome editing," a form of germline editing that includes transfer of edited material for gestation with the intent to generate a new human being possessing the potential to transmit the "edit" to future generations, is discussed in this chapter.
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From page 112... ...
. A similar debate is already under way regarding a related set of techniques -- mitochondrial replacement -- in which genetic disease carried by mitochondrial DNA is avoided by using healthy mitochondria from a donor.
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From page 113... ...
But as with PGD, some people find it unacceptable to terminate an ongoing pregnancy regardless of the predicted health of the future child. In these situations, for those who are aware they are at risk of passing on such a mutation, the use of heritable genome editing offers a potential avenue to having genetically related children who are free of the mutation of concern.
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From page 114... ...
, again increasing the likelihood of transmitting disease alleles. As our ability to treat children and adults with serious genetic diseases improves through both conventional and somatic genome-editing therapies, there may be a growing need to address concerns potential parents might have about passing along these diseases to their children.
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From page 115... ...
Couples with such diseases who want to have genetically related children might be future candidates for heritable genome editing because editing the defective gene in the germline could have therapeutic benefit in all tissues. Duchenne muscular dystrophy (DMD)
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From page 116... ...
edits. This situation is called "mosaicism," and it presents a significant challenge to the application of heritable genome editing in zygotes or embryos.
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From page 117... ...
. Potential Alternative Routes to Heritable Edits Editing the embryo genome is not the only potential way to achieve heritable genome modification.
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From page 118... ...
As discussed earlier, the numbers of cases of human germline editing to treat disease, if it were to be approved, would be very small, and there is little chance of any significant effects on the gene pool in the foreseeable future. It has also been proposed that any heritable genome editing should be restricted to making changes that occur naturally in the human population (i.e., converting deleterious disease-causing variant [mutant]
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From page 119... ...
This is still true, but more is being learned every year about the genetic regulatory circuits that control complex traits, and there is an ongoing need to consider the potential benefits and risks of heritable genome editing. Balancing Individual-Level Benefits and Societal-Level Risks One of the challenging characteristics of debates concerning heritable genome editing is that they require balancing possible benefits that accrue primarily to individuals (such as prospective parents and children)
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From page 120... ...
Access to heritable genome editing would be consistent with the broadest legal and cultural interpretations of parental autonomy rights in the United States. The desire to have genetically related children may arise from a variety of factors, ranging from a wish to see one's self or one's ancestors reflected in the appearance of the children to a belief in the need for a biological linkage in order to satisfy a sense of lineage, continuity, or even some form of immortality (Rulli, 2014)
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From page 121... ...
And the concept of procreative liberty has never been extended to a positive right to demand that government fund or even approve new reproductive technologies. Potential Risks Balanced against the possible benefits of heritable genome editing are a variety of potential risks.
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From page 122... ...
Although improvements in genome-editing technology are reducing the incidence of off-target events, and methods for assessing their rate, some approaches already approved for somatic therapies, are being developed, they have not yet reached the point at which clinical trials of heritable genome editing could be authorized. Before any such clinical trials are approved, it will be necessary to demonstrate that the editing procedures will not lead to any significant increase in unintended variants.
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From page 123... ...
. Others see a public health benefit in access to heritable genome editing because it might somewhat reduce the prevalence of many devastating diseases, such as Tay-Sachs and Huntington's disease.
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From page 124... ...
A "Natural" Human Genome and the Appropriate Degree of Human Intervention Among the social and cultural arguments against heritable genome editing are positions that support a preference for a "natural" genome. Although there is wide acceptance of human intervention in agriculture and medicine, some hold the view that the human genome is different and should be free of intentional manipulation because of some aspect of its naturalness, whether defined as "normal," "real," or otherwise determined largely by forces other than human intervention (Nuffield Council, 2015)
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From page 125... ...
Overall, from a scientific viewpoint, some conclusions about likely benefits and risks of heritable genome editing can be supported with a fair degree of certainty, while others remain uncertain and in need of further investigation and societal debate, calling for humility with respect to those conclusions. Assessing the probabilities of efficacy and risk is the focus of clinical trials, which can be viewed as a manifestation of the recognition of the limits of human knowledge.
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From page 126... ...
. Even if limited to preventing serious disease or disability, the prospect of using heritable genome editing triggers concern that purely voluntary, individual decisions can collectively change social norms regarding the acceptance of less serious disabilities (Sandel, 2004)
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From page 127... ...
Economic and Social Justice Recognizing that heritable genome-editing technology is unlikely to be used widely in the near future and that drastic transformation of the species or immediate changes in cultural norms are unlikely, some social justice arguments focus on the effects of the technology's being accessible only to a few rather than to too many. In this framing, the technology is another example of a society's allocating considerable resources to developing a
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From page 128... ...
Another concern is that if heritable genome editing were to become prevalent among those who are wealthier or better insured, it could change the prevalence of avoidable diseases between advantaged and disadvantaged populations and could permanently establish what Harris (2007) calls "parallel populations." While great inequality already exists, the argument continues, heritable genome editing would make a culturally determined inequality into one that is biological.
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From page 129... ...
Many of the attempts to introduce speed bumps or friction on the slippery slope in the evolution of genetic modification of humans have focused on the easily grasped linguistic/cognitive difference between a body/ individual and offspring/society, thereby establishing the distinction between editing of somatic and germline cells. Critics would claim that the
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From page 130... ...
Overall, slippery slope arguments do not depend on universal condemnation of the initial, most compelling applications of heritable genome editing. But while many think that regulation could establish effective speed bumps, proponents of slippery slope arguments raise the question of whether and how society can develop regulations that are sufficiently robust to quell the fear of a progressive move toward less compelling and more controversial applications.
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From page 131... ...
used for PGD. Heritable genome editing would be performed in conjunction with IVF and PGD, and thus could involve statutes and regulations that apply to those technologies.
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From page 132... ...
Salient instruments that have legal effect include the European Oviedo convention, which allows genetic engineering only for preventive, diagnostic, or therapeutic purposes and only when it is not aimed at changing the genetic makeup of a person's descendants, thus precluding heritable genome editing. Although signed by 35 nations, this convention is binding only on those 29 that ratified it (6 nations did not ratify it in full)
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From page 133... ...
. CONCLUSIONS AND RECOMMENDATION In some situations, heritable genome editing would provide the only or the most acceptable option for parents who desire to have genetically related children while minimizing the risk of serious disease or disability in a prospective child.
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From page 134... ...
A robust public discussion about the values to be placed on the benefits and risks of heritable genome editing is needed now so that these values can be incorporated as appropriate into the risk/benefit assessments that will precede any decision about whether to authorize clinical trials. But the FDA does not have a statutory mandate to consider public views on the intrinsic morality of a technology when deciding whether to authorize clinical trials.
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From page 135... ...
while the basic science evolves and regulatory safeguards are developed to satisfy the criteria set forth here. Heritable genome editing raises concerns about premature or unproven uses of the technology, and it is possible that the criteria outlined here for responsible oversight would be achievable in some but not all jurisdictions.
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From page 136... ...
authorities to review proposals for clinical trials of heritable genome editing, and therefore to drive development of this technology to other jurisdictions, some regulated and others not. 9 Consolidated Appropriations Act of 2016, HR 2029, 114 Cong., 1st sess.
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