scholarly journals Is selecting better than modifying? An investigation of arguments against germline gene editing as compared to preimplantation genetic diagnosis

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Alix Lenia v. Hammerstein ◽  
Matthias Eggel ◽  
Nikola Biller-Andorno

Abstract Background Recent scientific advances in the field of gene editing have led to a renewed discussion on the moral acceptability of human germline modifications. Gene editing methods can be used on human embryos and gametes in order to change DNA sequences that are associated with diseases. Modifying the human germline, however, is currently illegal in many countries but has been suggested as a ‘last resort’ option in some reports. In contrast, preimplantation genetic (PGD) diagnosis is now a well-established practice within reproductive medicine. Both methods can be used to prevent children from being born with severe genetic diseases. Main text This paper focuses on four moral concerns raised in the debate about germline gene editing (GGE) and applies them to the practice of PGD for comparison: Violation of human dignity, disrespect of the autonomy and the physical integrity of the future child, discrimination of people living with a disability and the fear of slippery slope towards immoral usage of the technology, e.g. designing children for specific third party interests. Our analysis did not reveal any fundamental differences with regard to the four concerns. Conclusion We argue that with regard to the four arguments analyzed in this paper germline gene editing should be considered morally (at least) as acceptable as the selection of genomes on the basis of PGD. However, we also argue that any application of GGE in reproductive medicine should be put on hold until thorough and comprehensive laws have been implemented to prevent the abuse of GGE for non-medical enhancement.

2007 ◽  
Vol 56 (3) ◽  
Author(s):  
Jacques Suaudeau

La diagnosi genetica pre-impiantatoria (Preimplantation genetic diagnosis o PGD) è una tecnica nella quale gli embrioni umani prodotti in vitro per le tecniche di fecondazione artificiale, vengono selezionati, nelle prime fasi di sviluppo, dal punto di vista genetico, tramite lo studio di uno o due blastomeri prelevati con una biopsia. Gli embrioni non affetti da malattie vengono poi trasferiti nell’utero. La PGD è stata introdotta agli inizi degli anni ’90 in alternativa alla diagnosi prenatale per coppie per le quali fosse alto il rischio di trasmettere un difetto genetico. Negli anni successivi è stata adoperata per altre indicazioni come l’individuazione delle anomalie cromosomiche, la ricerca delle aneuploidie, la selezione “sociale” del sesso, la selezione degli embrioni secondo il tipo di Human Leukocit Antigen (HLA) e l’individuazione di malattie genetiche ad esordio tardivo. Dai reports relativi all’uso della PGD nel mondo emergono, tuttavia, tre punti critici: il primo riguarda l’esattezza diagnostica, con la presenza di falsi positivi e falsi negativi; la seconda, la notevole perdita di embrioni umani nel processo; la terza, i risultati della PGD in termini di nascita di bambini sani. ---------- The preimplantation genetic diagnosis (PGD) is a technique in which early human embryos, obtained in vitro for artificial fertilization techniques, are genetically screened for selection, through study of one or two blastomeres taken by biopsy. The embryos, that are healthy, are transferred to uterus. The PGD has been introduced in the early 1990s as an alternative to prenata1 diagnosis for couples at high risk of transmitting a genetic defect. It has been subsequently extended to other indications as the individualization of chromosomal abnormalities, the research of the aneuploidies, the “social selection of sex”, the selection of the embryos according to the type of Human Leukocit Antigen (HLA) and the individualization of late-onset genetic diseases. But the reports concerning with the use of PGD in the world make clear that there are three critical points: the first deals with the diagnostic accuracy, with the presence of false positives and false negatives; the second, with the wide loss of embryos during the process; the third, with the outcomes of the PGD in terms of birth of healthy babies.


2017 ◽  
Vol 42 (12) ◽  
pp. 3-4
Author(s):  
Jozef Zalot ◽  
Tadeusz Pacholczyk ◽  

In August 2017, researchers at the Oregon Health and Science University announced that they had successfully used a gene editing technique known as CRISPR-Cas9 to repair disease-causing genes in human embryos. Some members of the scientific and medical communities have hailed the development as a way to ensure that life- threatening diseases are not passed on to future generations. But is gene editing always a good thing? The Catholic Church encourages scientific research that is ethical and serves the human good. In the future, CRISPR may be used to treat people with serious genetic diseases, such as hemophilia and sickle-cell anemia. However, for research on human beings to be ethical, it must be strictly therapeutic and must respect the dignity and sacredness of human life. Gene-editing techniques raise profound ethical challenges in both respects.


2019 ◽  
Vol 11 (4) ◽  
pp. 61
Author(s):  
Hille Haker

In The Future of Human Nature, Jürgen Habermas raises the question of whether the embryonic genetic diagnosis and genetic modification threatens the foundations of the species ethics that underlies current understandings of morality. While morality, in the normative sense, is based on moral interactions enabling communicative action, justification, and reciprocal respect, the reification involved in the new technologies may preclude individuals to uphold a sense of the undisposability (Unverfügbarkeit) of human life and the inviolability (Unantastbarkeit) of human beings that is necessary for their own identity as well as for reciprocal relations. Engaging with liberal bioethics and Catholic approaches to bioethics, the article clarifies how Habermas’ position offers a radical critique of liberal autonomy while maintaining its postmetaphysical stance. The essay argues that Habermas’ approach may guide the question of rights of future generations regarding germline gene editing. But it calls for a different turn in the conversation between philosophy and theology, namely one that emphasizes the necessary attention to rights violations and injustices as a common, postmetaphysical starting point for critical theory and critical theology alike. In 2001, Jürgen Habermas published a short book on questions of biomedicine that took many by surprise.[1] To some of his students, the turn to a substantive position invoking the need to comment on a species ethics rather than outlining a public moral framework was seen as the departure from the “path of deontological virtue,”[2] and at the same time a departure from postmetaphysical reason. Habermas’ motivation to address the developments in biomedicine had certainly been sparked by the intense debate in Germany, the European Union, and internationally on human cloning, pre-implantation genetic diagnosis, embryonic stem cell research, and human enhancement. He turned to a strand of critical theory that had been pushed to the background by the younger Frankfurt School in favor of cultural theory and social critique, even though it had been an important element of its initial working programs. The relationship of instrumental reason and critical theory, examined, among others, by Max Horkheimer, Theodor W. Adorno, and Herbert Marcuse and taken up in Habermas’ own Knowledge and Interest and Theory of Communicative Action became ever-more actual with the development of the life sciences, human genome analysis, and genetic engineering of human offspring. Today, some of the fictional scenarios discussed at the end of the last century as “science fiction” have become reality: in 2018, the first “germline gene-edited” children were born in China.[3] Furthermore, the UK’s permission to create so-called “three-parent” children may create a legal and political pathway to hereditary germline interventions summarized under the name of “gene editing.”In this article, I want to explore Habermas’ “substantial” argument in the hope that (moral) philosophy and (moral) theology become allies in their struggle against an ever-more reifying lifeworld, which may create a “moral void” that would, at least from today’s perspective, be “unbearable” (73), and for upholding the conditions of human dignity, freedom, and justice. I will contextualize Habermas’ concerns in the broader discourse of bioethics, because only by doing this, his concerns are rescued from some misinterpretations.[1] Jürgen Habermas, The Future of Human Nature (Cambridge, UK: Polity, 2003).[2] Ibid., 125, fn. 58. 8[3] Up to the present, no scientific publication of the exact procedure exists, but it is known that the scientist, Jiankui He, circumvented the existing national regulatory framework and may have misled the prospective parents about existing alternatives and the unprecedented nature of his conduct. Yuanwu Ma, Lianfeng Zhang, and Chuan Qin, "The First Genetically Gene‐Edited Babies: It's “Irresponsible and Too Early”," Animal Models and Experimental Medicine  (2019); Matthias Braun, Meacham, Darian, "The Trust Game: Crispr for Human Germline Editing Unsettles Scientists and Society," EMBO reports 20, no. 2 (2019).


Author(s):  
Rodrigo Ribeiro Arnt Sant’Ana ◽  
Clarissa Alves Caprestano ◽  
Rubens Onofre Nodari ◽  
Sarah Zanon Agapito-Tenfen

CRISPR-Cas9 technology allows the modification of DNA sequences in vivo at the location of interest. Although CRISPR-Cas9 can produce genomic changes that do not require DNA vector carriers, the use of transgenesis for stable integration of DNA coding for gene-editing tools into plant genomes is still the most used approach and it can generate unintended transgenic integrations, while Cas9 prolonged expression can increase cleavage at off-target sites. In addition, the selection of genetically modified cells from millions of treated cells, especially plant cells, is still challenging. These downfalls can be avoided with the delivery of preassembled ribonucleoprotein complexes (RNPs) composed of purified recombinant enzyme Cas9 and in vitro- transcribed guide RNA (gRNA) molecules in a protoplast system. We therefore aimed to develop the first DNA-free protocol for gene-editing in maize and introduced RNPs into their protoplasts with PEG 4000. We performed effective transformation of maize protoplasts using different gRNAs sequences targeting the inositol phosphate kinase gene and applying two different exposure times to RNPs. Using low-cost Sanger sequencing protocol, we observed an efficiency rate of 0.85 up to 5.85%, which is equivalent to DNA-free protocols used in other plant species. A positive correlation was displayed between exposure time and mutation frequency. Mutation frequency was gRNA sequence- and exposure time-dependent. In summary, we demonstrated the suitability of RNP transfection as an effective screening platform for gene-editing in maize. This efficient and relatively easy assay method for selection of gRNA suitable for editing of gene of interest will be highly useful for genome editing in maize, since genome size and GC-content are large and high in maize genome, respectively. Nevertheless, the large amplitude of mutations at target site requires scrutiny when checking mutations at off-target sites and potential safety concerns.


Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1029 ◽  
Author(s):  
Rodrigo Ribeiro Arnt Sant’Ana ◽  
Clarissa Alves Caprestano ◽  
Rubens Onofre Nodari ◽  
Sarah Zanon Agapito-Tenfen

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology allows the modification of DNA sequences in vivo at the location of interest. Although CRISPR-Cas9 can produce genomic changes that do not require DNA vector carriers, the use of transgenesis for the stable integration of DNA coding for gene-editing tools into plant genomes is still the most used approach. However, it can generate unintended transgenic integrations, while Cas9 prolonged-expression can increase cleavage at off-target sites. In addition, the selection of genetically modified cells from millions of treated ones, especially plant cells, is still challenging. In a protoplast system, previous studies claimed that such pitfalls would be averted by delivering pre-assembled ribonucleoprotein complexes (RNPs) composed of purified recombinant Cas9 enzyme and in vitro transcribed guide RNA (gRNA) molecules. We, therefore, aimed to develop the first DNA-free protocol for gene-editing in maize and introduced RNPs into their protoplasts with polyethylene glycol (PEG) 4000. We performed an effective transformation of maize protoplasts using different gRNAs sequences targeting the inositol phosphate kinase gene, and by applying two different exposure times to RNPs. Using a low-cost Sanger sequencing protocol, we observed an efficiency rate of 0.85 up to 5.85%, which is equivalent to DNA-free protocols used in other plant species. A positive correlation was displayed between the exposure time and mutation frequency. The mutation frequency was gRNA sequence- and exposure time-dependent. In the present study, we demonstrated that the suitability of RNP transfection was proven as an effective screening platform for gene-editing in maize. This efficient and relatively easy assay method for the selection of gRNA suitable for the editing of the gene of interest will be highly useful for genome editing in maize, since the genome size and GC-content are large and high in the maize genome, respectively. Nevertheless, the large amplitude of mutations at the target site require scrutiny when checking mutations at off-target sites and potential safety concerns.


2019 ◽  
Vol 19 (2-3) ◽  
pp. 226-232 ◽  
Author(s):  
Iñigo de Miguel Beriain ◽  
Emilio Armaza Armaza ◽  
Aliuska Duardo Sánchez

Human germline gene editing has ignited wide-ranging debates on the ethical and legal issues involved. The text of the Oviedo Convention is particularly relevant here, as it remains the only international legally binding instrument on the protection of human rights in the biomedical field which considers human genome modification. However, it is often misinterpreted. Indeed, most of the academic literature assumes that Article 13 forbids germline gene editing. This article seeks to demonstrate that this belief is mistaken. To this purpose, it develops a general analysis of the Convention, its Explanatory Report, and its historical background. As a result, it argues that the Convention does not veto genetic editing for basic research purposes, but only its clinical application on human embryos to be transferred into a womb. Nevertheless, it recommends a revision of the clause according to the original intention of the Convention.


Author(s):  
N.A. Altinnik , S.S. Zenin , V.V. Komarova et all

The article discusses the factors that determine the content of the legal limitations of pre-implantation genetic diagnosis in the framework of the in vitro fertilization procedure, taking into account international experience and modern domestic regulatory legal regulation of the field of assisted reproductive technologies. The authors substantiates the conclusion that it is necessary to legislate a list of medical indications for preimplantation genetic diagnosis, as well as the categories of hereditary or other genetic diseases diagnosed in the framework of this procedure.


Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 701
Author(s):  
Ovidiu Bîcă ◽  
Ioan Sârbu ◽  
Carmen Iulia Ciongradi

This article reviews the latest information about preserving reproductive potential that can offer enhanced prospects for future conception in the pediatric male population with cancer, whose fertility is threatened because of the gonadotoxic effects of chemotherapy and radiation. An estimated 400,000 children and adolescents aged 0–19 years will be diagnosed with cancer each year. Fertility is compromised in one-third of adult male survivors of childhood cancer. We present the latest approaches and techniques for fertility preservation, starting with fertility preservation counselling, a clinical practice guideline used around the world and finishing with recent advances in basic science and translational research. Improving strategies for the maturation of germ cells in vitro combined with new molecular techniques for gene editing could be the next scientific keystone to eradicate genetic diseases such as cancer related mutations in the offspring of cancer survivors.


2021 ◽  
Vol 7 (3) ◽  
pp. eaba1028
Author(s):  
Rachel S. Riley ◽  
Meghana V. Kashyap ◽  
Margaret M. Billingsley ◽  
Brandon White ◽  
Mohamad-Gabriel Alameh ◽  
...  

Clinical advances enable the prenatal diagnosis of genetic diseases that are candidates for gene and enzyme therapies such as messenger RNA (mRNA)–mediated protein replacement. Prenatal mRNA therapies can treat disease before the onset of irreversible pathology with high therapeutic efficacy and safety due to the small fetal size, immature immune system, and abundance of progenitor cells. However, the development of nonviral platforms for prenatal delivery is nascent. We developed a library of ionizable lipid nanoparticles (LNPs) for in utero mRNA delivery to mouse fetuses. We screened LNPs for luciferase mRNA delivery and identified formulations that accumulate within fetal livers, lungs, and intestines with higher efficiency and safety compared to benchmark delivery systems, DLin-MC3-DMA and jetPEI. We demonstrate that LNPs can deliver mRNAs to induce hepatic production of therapeutic secreted proteins. These LNPs may provide a platform for in utero mRNA delivery for protein replacement and gene editing.


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