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Human genome editing

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Subject and objective of the study

In recent years, the latest variant of genetic engineering – the so-called genome editing (including methods based on the CRISPR-Cas9 system) – has triggered a veritable research and development boom in plant and animal breeding as well as in human medicine due to its easy and versatile applicability. Because genome editing allows the targeted insertion of genes into the genome and the modification of genome sequences in basically all types of cells in a targeted manner, many researchers expect a relevant decrease of unintended side effects and solutions for the low efficiency of some approaches. So far, these problems have slowed down development in the field of somatic gene therapy (this approach aims to introduce therapeutic gene sequences into those cells that build our body and organs, but not into germline cells, so that these sequences are not passed to offspring). In particular, the possibility of modifying cellular gene sequences is expected to expand gene-based therapeutic options to previously unaddressable hereditary diseases. Even modifications of the germline, i. e. permanent, hereditary interventions in the human genome, were made possible by genome editing in the first place. In autumn 2018 a Chinese scientist announced the birth of twins whose genomes had been deliberately altered during in vitro fertilisation. This triggered an intensive debate that involves ethicists and scientists as well as politicians and the public debate, going far beyond the case - which has since been classified as unethical and illegal by a court in China - to address also the future handling of possible germline interventions in general.

The objective of TAB's monitoring project was to provide an interdisciplinary presentation of the status quo regarding both potential germline therapies and somatic gene therapies via genome editing procedures. While the topic of germline therapy focused on analysing the previous and ongoing ethical and legal as well as scientific and public discourse, the topic of somatic gene therapy mainly concentrated on determining the scientific-medical status quo. The study also took into account parallel investigations on different aspects of the topic that were conducted by ethics councils at the national and European level, within the framework of the BMBF's funding programmes on the ethical, legal and social aspects of genome editing, and by scientific academies and TA institutions abroad. In order to timely inform the members of parliament, an expert discussion on the interim results of the study was held in the German Bundestag in spring 2018.

Key results

Germline therapy

The possibility to modify the human genome already in gametes or fertilised eggs is at the centre of public and scientific debate. The debate about the medical, legal and ethical implications of germline interventions was largely theoretical until reports on first laboratory experiments on very early (single-cell) embryos were published in 2015. The debate was fuelled particularly when news about an experiment in China emerged in 2018 that had resulted in the birth of twins. The experiment, which aimed to protect the children from infections with HIV by modifying their genome, was condemned almost unanimously across the world, because the commensurability as well as the success of the intervention were questioned and a number of ethical and legal principles was violated.

Several ethics councils, including the German Ethics Council and the British Nuffield Council on Bioethics, point out that the prerequisites for germline interventions are not yet given, but do not raise principal objections. However, the number of realistic application scenarios is very small and the uncertainty regarding options for their implementation is high. If research were to be initiated in Germany that could point the way to germline interventions, the legal ban on experiments on embryos would have to be amended first. Such a step would have to be preceded by a broad societal debate and forming of opinion. At the international level, agreements could be worked towards observing research on germline interventions by competent institutions and to refrain from clinical trials until the requirements regarding medical safety, ethical justifiability and societal acceptance are fulfilled.

Somatic gene therapy

Applications of genome editing in somatic cells have so far been discussed mainly in specialist circles. First clinical trials have been started addressing monogenic diseases or some cancer types, for example. In Germany, a patient with β-thalassemia is being treated. The more targeted insertion of genes into the genome is intended to make the therapies more efficient and safer, moreover, it is theoretically possible to address diseases that cannot be treated with previous gene therapies (e.g. Huntington's disease or Leber congenital amaurosis type 10, the most common form of hereditary blindness). However, (in)efficient gene transfer remains a challenge, and unintended, potentially serious damage to the genome (off- or on-target effects) and immune responses to the editing tools (derived from bacteria) may occur. An issue to consider is also equitable access to gene therapies, as the costs likely will remain high.

For somatic gene- and cell-based therapies there are tangible opportunities for political action in terms of public support for research and development (R&D). Apart from direct research funding, such support can encompass for example tax benefits for R&D investments and mega-fund models for financing high-risk but potentially high-profit projects. Given the high costs of therapies, existing reimbursement models could be supplemented with performance-based models and the effect of innovation incentives on drug development for rare diseases could be investigated more closely.

Publications


Genome Editing am Menschen. Endbericht zum Monitoring.
Albrecht, S.; König, H.; Sauter, A.
2021. Büro für Technikfolgen-Abschätzung beim Deutschen Bundestag (TAB). doi:10.5445/IR/1000141083Full textFull text of the publication as PDF document
Human genome editing. TAB-Fokus.
Albrecht, S.; König, H.; Sauter, A.
2021, September. Büro für Technikfolgen-Abschätzung beim Deutschen Bundestag (TAB) Full textFull text of the publication as PDF document
Genome Editing am Menschen. TAB-Fokus.
Albrecht, S.; König, H.; Sauter, A.
2021, September. Büro für Technikfolgen-Abschätzung beim Deutschen Bundestag (TAB) Full textFull text of the publication as PDF document