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Office of Technology Assessment at the German Bundestag Office of Technology Assessment at the German Bundestag

Information on the project

Human genome editing

Thematic area: Biomedical technologies
Analytical approach: Monitoring
Topic initiative: Committee on Education, Research and Technology Assessment
Status: ongoing
Current project phase: Preparation of external expertise
Duration: 2017 till 2018

Background and central aspects of the topic

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 boom in plant and animal breeding as well as in human medicine due to its easy and versatile applicability. Because genome editing allows to modify genome sequences in basically all types of cells in a targeted manner, many researchers expect a relevant decrease of unintended side effects which, so far, 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 germ cells, so that these sequences are not passed to offspring). As a consequence, an expansion of gene-based therapeutic options is expected. Meanwhile, even modifications of the germline, i. e. permanent, hereditary interventions in the human genome, are no longer beyond the realm of possibility. At the beginning of 2015, reports on corresponding experiments by Chinese scientists (though carried out in non-viable embryos) provoked an intensive debate among scientists and ethicists as well as a– to a certain degree – political and public debate which has been additionally heated up by further experiments on embryos (i. a. in the United Kingdom).

In Germany, in summer 2015, the Interdisciplinary Research Group »Gene Technology Report« of the Berlin-Brandenburg Academy of Sciences and Humanities presented a statement on a first evaluation of and for further dealing with human genome editing, and endorsed an international moratorium on interventions in the human germline. The German National Academy of Sciences Leopoldina, the National Academy of Science and Engineering acatech, the Union of the German Academies of Sciences and Humanities as well as the German Research Foundation (DFG) followed with a similar statement. The institutions did not call for a general moratorium on research in this field, but rather for a further clarification regarding potential risks and opportunities of the procedure as well as for a debate in society with regard to the ethical and legal issues involved in germline therapy. Since then, this debate has been fostered by the German Ethics Council in several events, partly together with the Leopoldina and/or the DFG, partly in sessions with ethics councils of other countries – including the British Nuffield Council on Bioethics which developed a particularly comprehensive work programme on genome editing.

In February 2017, the US National Academy of Sciences, Engineering, and Medicine presented a detailed report on its ‘consensus study’ on human genome editing. This report outlined criteria for a strict regulatory framework under which clinical trials for germline therapies might be permitted, but declined enhancement applications at this point in time. In March 2017, the European Academies' Science Advisory Council (EASAC) – domiciled at the Leopoldina – published a policy report on all current areas of application of genome editing (»Genome editing: scientific opportunities, public interests and policy options in the European Union«). The recommendations regarding potential applications in humans underline the need for further research, taking into consideration existing legal and ethical rules and procedures.

Also in March 2017, the Leopoldina presented a discussion paper by eleven authors (»Ethical and legal assessment of genome editing in research on human cells«). In the paper, the authors support the »use of genome editing in research on human embryonic development«, »research on germline gene therapies and effects« as well as the »use of embryos for research purposes«. Such research would require a change of legislation with respect to the German Embryo Protection Act (»Embryonenschutzgesetz«).

Objectives and approach

A larger interdisciplinary presentation of the topic »Human genome editing« in German is not available so far. Since autumn 2016, the German Federal Ministry of Education and Research (»BMBF«) has been funding seven interdisciplinary research projects and five retreats with regard to »ethical, legal and social aspects of modern genome editing procedures and their application«, half of which are dealing with issues of human medicine. After the projects will be completed in the end of 2019, a multifaceted and comprehensive basis of information for further societal and political discussion in Germany regarding the perspectives and challenges of genome editing in humans (as well as in agriculture) will be available. Moreover, for 2019, a TA study on different applications dealing with the topic of genome editing by the Swiss equivalent of the TAB – TA-SWISS – is to be expected for which an invitation to tender was issued in December 2016.

These ongoing parallel activities have been taken into consideration with regard to the objectives and design of the TAB project in order to be able to offer the 19th German Bundestag a valuable basis of information in 2018. The objective of the study is to determine the current status quo regarding both germline therapy and somatic gene therapy via genome editing procedures.

As the two fields of application are very different with regard to the relevant scientific-technological, medical, bioethical and legal questions as well as the controversial issues involved, two different approaches and focuses have been chosen: While the topic of germline therapy focuses on analysing the previous and ongoing ethical and legal as well as scientific and public discourse, the topic of somatic gene therapy shall mainly concentrate on determining the scientific-medical status quo. The objective is to provide compact presentations of the two application fields as a basis of information for foreseeable future debates regarding a potential adaptation of the Embryo Protection Act as well as regarding issues of intensifying research and development funding of somatic gene therapy approaches, e. g. for cancer therapy.

Germline therapy: ethical and legal discourse analysis – between application scenarios and permanent ban

After genome research has shown more and more clearly the complexity of the interaction between genetic variants and environmental factors, most researchers considered heritable interventions in the human germline to be irresponsible. That targeted alterations of genetic variants in cells (including fertilised eggs) have now been enabled by genome editing techniques would not alleviate the risk of unintended outcomes from these complex interactions. For this reason, it was quite surprising that genome editing for the inheritable modification of human genomes have become a key topic of scientific and ethical debates. In the context of the debate, e. g. at the Annual Meeting 2016 of the German Ethics Council, it has become obvious that in view of today’s state of knowledge only few tangible medical germline applications are conceivable at all. Besides medical applications, the topic of enhancement/designer babies plays a rather significant role at the international level, but also in Germany. However, there are only few plausible and tangible scenarios for such non-medical applications, as too little is known so far about the genetic basis of such complex traits like intelligence or appearance.

Moreover, in Germany, the Embryo Protection Act clearly stipulates a ban on any interventions in embryos for research purposes. Nevertheless, it might be necessary to adapt the legislative text to the new scientific and technological developments in order to close regulatory gaps. According to experts (Prof. Taupitz), these gaps consist, e. g., in the use of genome-edited somatic cells for producing (via induced pluripotent stem cells) sperm cells or oocytes in vitro for fertilisation, as well as with regard to the sufficient effectiveness of embryo protection or the ban on germline interventions, e. g. with respect to non-viable embryos.

Research questions: For germline therapy, questions are raised particularly regarding the medical justifiability, potential risks and ethical acceptability, the necessity of a review and revision of legal requirements in Germany and options for regulation at the international level.

Somatic gene therapy: scientific-medical status quo with regard to risks and opportunities

Still, somatic gene therapy is not a routine procedure, but mostly is in the research or trial phase. The main fields of application are monogenic diseases and cancer therapies by influencing the immune system. So far, it has been applied mainly in the context of clinical trials or experimental therapies.

Compared to previous approaches/procedures, somatic gene therapy via genome editing does not raise fundamentally new ethical or legal questions. Here, the main focus is on improving already pursued approaches (e. g. the repair of defective genes instead of introducing additional healthy gene copies) as well as on the potentials and risks of possible new strategies. This might include therapies for hereditary diseases that are not caused by a non-functional gene, but by functionally altered genes and their products. Moreover, (more) complex modifications in terms of reprogramming of immune cells for cancer therapy are imaginable.

Research questions: With regard to somatic gene therapy, the focus is on determining the scientific-medical status quo including the safety issues involved and the resulting need for research.

Project progress

In order to discuss the research questions concerning germline therapy, two external expert analyses have been commissioned by the German Bundestag. The objective is to trace and analyse the ongoing ethical and legal as well as scientific and public debate. Scenarios of medical applications (including ones that may provide alternatives to, or may be used in combination with, pre-implantation genetic diagnosis) as well as visions of non-therapeutic »genetic enhancement« applications shall be critically examined. In this context, particular attention is paid to the issues of regulatory gaps and international governance of research. Based on a concise presentation of the German legal situation by international comparison as well as of potential application scenarios, the project aims at extracting arguments, positions and options for action from the national and international discussions. These results will be summarised in a comparative overview, i. a. with regard to the question of whether national regulation is appropriate and with a view to existing alternatives at the supranational level.

Another external expert analysis has been commissioned to provide an overview of the most important research approaches and objectives of somatic gene therapy via genome editing procedures, including the safety issues involved and the need for research related to these issues. In this context, it shall also be discussed whether existing oversight and regulatory approaches for research (e. g. ethics commissions) are considered to be sufficient and effective.