By Sophie Balmer, PhD
Over the past few weeks, the scientific community has been overwhelmed with major advances in human embryonic research. Whether researchers report for the second time the use of Crispr to edit the human germline or extend the conditions of in vitro culture of human embryos (also here), these issues have been all over the news. However, as all topics can not be raised in only one post, therefore, I will focus on genome editing studies.
About a year ago, one research group in China reported the first genome editing of human embryos using Crispr technology. Although these embryos were not viable due to one additional copy of each chromosome, this study quickly became highly controversial and raised strong concerns. The public and scientific communities questioned whether editing the human germline for therapeutic benefits was legitimate, leading to numerous ethical discussions. A few of weeks ago, a second study reported genome editing of embryos reinforcing the debate around this issue. Additionally, several research proposal involving genomic modification of healthy human embryos’ DNA have been validated recently in other countries. In this post, I want to address several questions. What are the possible advances or consequences of such work? What is the current legislation on human genome editing worldwide? Are these studies as alarming as what is written in some newspaper articles?
The emergence of the Crispr technology a few years ago has revolutionized the way scientists work since this method greatly improves the efficiency of DNA alteration of model organisms. However, this powerful tool has also raised many concerns, notably on the possibility to easily tweak the human genome and generate modified embryos.
In the eyes of the general public, this kind of experiment resonates with science fiction books or movies. Because of the high potential of this technique, it is crucial to inform everyone correctly to avoid clichés. Recently, one of my favorite comedian and television host John Oliver depicted in a very bright and amusing way how small scientific advances are sometimes presented in the media. Although the examples he uses are dramatic, every scientific breakthrough gets its share of overselling to the public. In the case of gene-editing of human embryos, pretending we are about to use eugenics principles to engineer babies and their descendants with beneficial genes is pure fiction. However, to prevent any potential malpractice from happening, clear ethical discussions and regulations need to be established and then explained to the public to prevent misunderstanding of these issues.
Within the scientific community, last year’s results triggered the need for new discussions and regulations on human cloning. Modifying the genome of human embryos involves modifying the germline as well, leading eventually to the transmission of the genetic alteration to future generations. However, the consequences of such transmission are unknown. Potentially, this could resolve a number of congenital genetic diseases for the individual him/herself and be used for gene therapy but would result in generations of genetically modified humans.
Because of cultural and ethical differences between countries, the legislation (if there is any) around working with human embryos or cells derived from human embryos (hESC for human embryonic stem cells) is variable. International ethical committees have only been able to establish guidelines as instituting international laws on human cloning is impossible. Ultimately, each country is responsible for enforcing these rules. Most countries and international ethics committees agree on a ban on reproductive and therapeutic human cloning. Moreover, following last year published experiments, a summit held in December 2015 gathered experts from all around the world. The consortium concluded that gene-editing of embryos used to establish pregnancy should not be performed (for now) and to follow up on all-related issues, new sets of guidelines are coming out imminently.
Still, it seems difficult to get an idea of the consensus depending on the countries in which scientists perform experiments. There is range of possibilities when working with human samples: some countries completely prohibit any manipulation of human embryos or hESC while others authorize genetic modification of the embryo for research purposes only under specific conditions. In between several nations authorize research exclusively on already derived lines of hESC and others authorize derivation of hESC but no manipulation of the embryos themselves.
Besides these general rules and as of today, three countries have approved proposals for gene-editing of human embryos: China, the UK and Sweden. Research proposals in both European countries have authorized Crispr targeting of specific genes in healthy human embryos to assess the function of these genes during early human development. However, these embryos can not be used for in vitro fertilization (IVF) and have to be destroyed at the end of the study. The purpose of these studies would be to confirm what has been described in hESC and in mammalian model systems and contribute to our knowledge of human development.
On the other hand, both published studies from China focused on Crispr targeting towards clinical therapies of an incurable blood disease or HIV. The overall purpose of such projects is to test the use of the Crispr technology for gene therapy. Although rendering embryos immune to several diseases using Crispr is an attractive possibility, it seems more urgent to probe the validity of the technique in humans and assess whether the mechanisms of human embryonic development are similar to what has been hypothesized. Gene therapies have already been successfully attempted in humans using other techniques to modify the genome. Yet, the modifications were targeted towards specific cells in already-born individuals. Again, modifying the genome of embryos implies that the mutation will be inherited in future generations and is in a large part the reason of this debate. Moreover, Crispr targeting still leads to unspecific modification of the genome, although very promising results show that newly engineered cas9 could lead to very specific targeting. The consequences of such off-target modification are unknown and could be disastrous for the following generations.
Overall, no research proposal dares to consider genetically modified embryos to establish pregnancy but as research moves faster, increasing demand for ethical discussion and regulations are brought forward. As more studies come out, it will be interesting to follow the evolution of this debate. Additionally, informing clearly the population of the possibilities and outcomes of ongoing projects should be a priority so that they can give an informed consent towards such research. In any case, a clear boundary needs to be established between selecting the fittest embryo by pre-implantation genetic diagnosis, which is routinely performed for IVF and playing the sorcerer’s apprentice with human embryo’s