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Call for a moratorium on germ line experiments in humans

Modern genetic engineering tools enable genes to be modified in a genomic context in living cells. Genome surgery unlocks enormous potential for the treatment of genetic diseases, but it could also be misused for the uncontrolled manipulation of the human genome. An interdisciplinary working group of German scientists is calling for a moratorium on human germ line experiments to provide a space to define the opportunities and risks of this new technology more clearly.

Genome surgery © EJ, modified from scienceboard.net

Scientists refer to these new methods as "genome surgery", "gene editing" or "genome engineering". They facilitate, with unprecedented accuracy and precision, the targeted and permanent alteration of hereditary factors encoded in the DNA of the genome in human cells. This means that they could potentially correct and halt the devastating effects of diseases caused by a mutation in perhaps just one of a person's many DNA base pairs. One of these new methods is called CRISPR-Cas9, and is an easily manageable tool that can be used for changing a DNA sequence at exact locations on a chromosome. [CRISPR stands for "clustered regularly interspaced short palindromic repeats" and Cas9 for "CRISPR-associated protein 9".] The technology is now used in countless laboratories around the world, in basic research and animal and plant genetics, as well as increasingly in animal experiments and human cell cultures. The research is aimed at making the technologies suitable for repairing mutations associated with hereditary diseases, which would then lead to a cure.

As these "gene editing" methods become more refined, they can be used for more than just specifically modifying somatic cells. Improved versions of the methods have the potential to modify germ line cells and repair a mutation that would otherwise result in severely disturbed gene function. A paper published by a Chinese research group in May 2015 on the editing of the genome of human embryos, suggests that germ line modification will soon be feasible (Liang, P. et al, 2015. Protein and Cell 6 (5): 363-372). However, the paper has sparked a debate about the ethical implications of this kind of research. Liang and his colleagues have attempted to dissipate concerns by stressing that they only applied the CRISPR/Cas9 method to non-viable embryos that would not have resulted in live births, hence excluding any permanent genetic modification of a human being and his or her offspring. However, many European and American geneticists are concerned that such experiments could lead to human genome surgery taking place before the ethical, legal and social ramifications are addressed.

A moratorium on human germ line experiments

Prof. Dr. Jens Reich, Max Delbrück Centre for Molecular Medicine, Berlin-Buch. © MDC/ David Ausserhofer

The Interdisciplinary Research Group Gene Technology Report (IAG) of the Berlin-Brandenburg of Sciences and Humanities has published an opinion paper on these issues entitled "Human genome surgery – towards a responsible evaluation of a new technology". The IAG consists of renowned German scientists from the fields of medicine, life sciences, ethics, law, sociology and philosophy, and is a long-term monitoring project which addresses current developments in genetic engineering in Germany. The group of researchers has evaluated the technology's ethical, legal and social consequences and come up with recommendations for action.

Jens Reich, the renowned molecular biologist and former GDR civil rights activist, directed the analysis, which states that, in principle, the IAG is in favour of research into these new methods that are very promising for the medical sector. However, for the time being the IAG is totally opposed to gene surgery experiments on the human germ line, which the new methods have made possible. The IAG supports the call for a moratorium and recommends using the moratorium period to debate the experimental, ethical and legal aspects of germ line therapy in an open, transparent and critical manner. This call for a moratorium was triggered by a paper published in "Nature" in March 2015, written by a number of prominent American scientists, including genetic engineering pioneers and Nobel Laureates David Baltimore and Paul Berg.

Physicians are keen to use "gene editing" methods such as CRISPR/Cas9 to modify germ cells because of their potential to cure hereditary diseases by repairing the genes that cause them. Most hereditary diseases manifest during early development phases. It is believed that germ line therapies, which involve editing one or several cells and can be done at the time of in vitro fertilisation, are much simpler than somatic gene therapies which may have to reach billions of cells in a single organ. In addition to the inherent faultiness of the method (which will diminish in the future, but never be completely excluded), a major ethical problem associated with germ cell genome surgery is that irreversible genetic interventions may have an effect on future generations. Obviously it is impossible to obtain consent from those concerned. However, at the moment we only have limited knowledge of the multiple functions of genes. Correction of a "diseased" gene variant could potentially affect hitherto unknown areas.

Loopholes in the prohibition of germ line interventions

Prof. Dr. Jochen Taupitz, Institute for German, European and International Medical Law, Public Health Law and Bioethics, University of Mannheim © German Ethics Council

Germ cell therapy is prohibited in Germany and any infringements are subject to sanctions. Under the German Embryo Protection Act, artificially altering any genetic information in a human germ line and using a human germ cell with artificially altered genetic information for fertilisation are both prohibited. However, altering the genetic information of germ cells where use for fertilisation has been ruled out is exempt from the ban.

Jochen Taupitz, a legal scholar at the University of Mannheim, Vice Chairman of the German Ethics Council and one of the experts of the IAG analysis, points out the loophole in the legal definition: early embryos, for example, where it is difficult to say which cells will become germ line and which will become somatic cells, are legally controversial. "In terms of definitions, germ line is not the same as embryo protection, and alterations to the germ line may be authorised or banned without protecting or harming an existing embryo."

It is unclear whether the research carried out in China would have been allowed in Germany. On the one hand, the Chinese researchers used non-viable embryos; on the other, fertilisation was carried out or at least attempted. This is exactly why the Embryo Protection Act was put in place. The Chinese experiments did not produce any new evidence that was not already known from animal experiments. At best, scientists do experiments like these as a profile-raising exercise; at worst, they are a hubristic attempt to test what the scientists believe is feasible, ignoring potential risk. Under the guise of well-intentioned therapeutic aims, such research could open the door to eugenics geared towards genetically "improving" human beings.

The IAG recommends using the moratorium period to debate the opportunities and risks of genome surgery methods in greater depth. All ethical and legal aspects of germ line therapy must be discussed openly and critically and the opportunities and risks of these technologies need to be more clearly defined in order to be able to make recommendations for future legislation.

Human genome surgery – towards a responsible evaluation of a new technologye. Analysis by the Interdisciplinary Research Group Gene Technology Report, Berlin-Brandenburg Academy of Sciences and Humanities, 2015, 27 pages, ISBN 978-3-939818-58-8

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/call-for-a-moratorium-on-germ-line-experiments-in-humans