Bioethics. Группа авторов

obtained. In addition, when prospective parents are both heterozygous for a dominant genetic disorder, the risk of transmission is as high as 75%, hence the chances of finding mutation‐free embryos significantly low. Another case where PGD is not effective is when both parents are homozygous for a recessive genetic disorder, meaning that they both carry two variants of the disease‐causing gene (Nuffield Council on Bioethics 2016; Vassena et al. 2016). In such cases, genome editing could represent an alternative to PGD and a new reproductive option for some prospective parents: mutations potentially leading to monogenic diseases would be corrected in embryos created with IVF prior to the transfer in utero or directly onto prospective parents’ gametes prior to fertilisation. Lastly, gene editing could replace PGD for women at risk of transmitting mitochondrial diseases as mitochondrial DNA mutations present in oocytes² could be corrected in the embryo (Vassena et al. 2016).

In the following section, I briefly present the debate on genome editing technologies applied to human embryos and I show how these technologies could be used as an alternative to PGD for the aforementioned cases where PGD is not effective. In [the] “Assisted reproduction and PGD, or assisted reproduction and CRISPR?” section, I present the moral reasons in favour of and against introducing genome editing as an alternative to PGD. In particular, I present arguments in favour of using genome editing instead of, or as an alternative to, PGD, and argue that some of the moral arguments against PGD would not be applicable to genome editing. I conclude, ad interim, that such arguments offer a prima facie case in favour of introducing genome editing as a new reproductive option, given that safety concerns are thoroughly assessed. In [the] “Curing embryos, society or prospective parents?” section, I turn to other arguments on the ethics of introducing genome editing as a new reproductive option and argue that there are additional questions that need to be carefully addressed. I conclude that introducing genome editing in the context of assisted reproduction would have some benefits, but that concerns regarding the equality of access to assisted reproduction and the allocation of scarce resources should be addressed beforehand.

CRISPR and Assisted Reproduction

      Gene‐editing technologies have been around for over a decade. Zinc finger nucleases (ZFNs) and transcription activator‐like effector nucleases (TALENs), two gene‐editing technologies, were discovered in 2005 and 2010 respectively (Nuffield Council on Bioethics 2016). ZFNs and TALENs are relatively precise techniques, but have the disadvantage that they need engineered proteins to target specific sequences of the DNA, a procedure that requires time and resources (Nuffield Council on Bioethics 2016).

      A new gene editing technique sparked debate early in 2015 due to its application on non‐viable human embryos by a group of Chinese scientists (Baltimore et al. 2015; Lanphier and Urnov 2015). The technique in question is CRISPR/Cas9, an RNA‐guided tool composed of two parts: clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR‐associated protein 9 (Cas9). CRISPR/Cas9 makes use of a naturally occurring defence mechanism that bacteria use to avoid harmful infections caused by pathogenic organisms (e.g. viruses). The RNA tool (CRISPR) functions as a guide for the Cas proteins to target specific parts of the genome, which are subsequently cut by the Cas proteins. These cut strands can be exploited to modify the nucleotide sequence of DNA and to insert genes at the cut site. The application of this technique to human embryos and human gametes (i.e. oocytes and sperm cells) has been widely criticised for a number of issues, but chiefly for its potential to introduce inheritable changes in the human genome (germline modification). Indeed, the issue of germline modification has catalysed the attention of many scientists and ethicists (Brokowski et al. 2015; Lander 2015; Lanphier and Urnov 2015).

This paper focuses on PGD and CRISPR³ applications to the field of assisted reproduction. In particular, it focuses on CRISPR as a potential alternative to PGD. CRISPR could represent a tool to avoid the occurrence of genetic diseases in future children through the modification of the genetic makeup of embryos created with IVF from couples with a known risk of transmitting such genetic diseases. Since using CRISPR on early embryos could give to prospective parents who are either affected by monogenic diseases or who are carriers of them a chance to avoid the transmission of these diseases to their offspring, this particular application of CRISPR can be considered a new reproductive option for parents who want to have genetically related children.

Assisted Reproduction and PGD, or Assisted Reproduction and CRISPR?

Research on human embryos with CRISPR technology is still at an early stage and only [a] few experiments have been carried out thus far (Vassena et al. 2016). Despite this, the issue of allowing clinical research has been discussed recently (Gyngell et al. 2016; Vassena et al. 2016; Reyes and Lanner 2017). The two main precautionary reasons that have been advanced against clinical applications of genome editing on human embryos or gamete cells are concerns regarding introducing changes in the human germline and safety questions. Many scholars and members of the public consider germline modifications unethical and a “line that should not be crossed” (Collins 2015; for a discussion of this claim, see: Camporesi and Cavaliere 2016). The worry is that edited embryos will pass their edited genome on to future generations, thus introducing changes in humanity’s gene pool. While it is of fundamental moral importance to consider the impact of present actions that could potentially have an impact on future generations, it seems reductive to limit these precautionary reflections to changes introduced with genome editing technologies on reproductive cells and embryos. In particular, those who worry about germline modifications via CRISPR and other genome editing technologies maintain that there is something exceptional in changes introduced technologically in our genomes via genome editing (and indirectly into the genomes of our offspring). The worry about germline modification encompasses a number of concerns, including the view that the human genome should be preserved intact as a “common heritage of our humanity” (cf. UNESCO statement against cloning, UNESCO 1997); the view that would be ethically problematic to change the germline of future generations “without their consent” (Collins 2015); and concerns regarding the safety of the technique not only for the child born thanks to its aid, but also for the child’s children (more about this below and in [the] “Reproductive autonomy, child welfare and the interests of society” section). This first view misrepresents partially the natural history of humankind and how past and present humanly introduced innovations shape future generations (Buchanan 2011; Harris 1992). The introduction of agriculture, for instance, played a role not only in shaping our environment, but has fundamentally changed our genomes. The same could be said about technologies such as literacy and numeracy, which laid the foundations for technological innovations that have significantly changed us (Buchanan 2008, 2011). In other words, from a moral point of view, it seems irrelevant which means are used and whether inheritable changes are introduced with genome editing technologies or caused by other technological innovations, unless one is able to show the moral exceptionality of using genome editing technologies (Harris 2010). In addition to this, focusing solely on technical means to introduce changes the human gene pool overlooks how other policies (such as those dealing with greenhouse gas mitigation), innovations (such as those in the field of agriculture) and human habits could have similar effects (i.e. introduce changes in the gene pool) with potentially much more serious consequences (Dupras et al. 2014). The view that emphasises the need to ask the consent of future generations, as argued by Harris (2016), fails to state how such consent could be obtained. Most procreative decisions affect future generations, but it is unclear how and why the consent of future offspring should be obtained prior to act (Harris 2016).

      The other argument against allowing genome editing for clinical uses is concern for the safety of future offspring (and of this offspring’s offspring). At this stage, safety is indeed an issue and the efficiency of genome editing on embryos remains low, with mosaic embryos (i.e. embryos that have abnormal numbers of chromosomes in certain cells resulting in genetically different cells coexisting in the same organism) being the main known drawback of these technologies (Vassena et al. 2016). Despite this, some studies have proven the feasibility of gene editing in animals (Heo et al. 2014;