On Monday, 26th November, the story that Chinese scientists in Shenzhen have performed CRISPR editing of human embryos for reproductive genomic editing came to light. The initial reporting of the story was patchy, without the normal scientific process of published papers accompanied by extensive data and peer review. This lack of facts makes it likely that more details about this story will emerge over the coming days.
The fact that researchers could perform genome editing in the embryo has long been a real possibility, but due to tight regulations in European countries, such experiments do not occur in Europe. This blog post provides a short background to CRISPR technology, and some thoughts to help reporters and the general public understand the context better.
There are three main points I want to convey. The first is that this type of science needs strong regulation which society can be confident in. The second is that I believe that this was an inappropriate study that is almost certainly unethical in a European setting. Finally the specifics of the study have been poorly thought through, and do not have the standard rigour of scientific research.
CRISPR is an acronym used to describe a remarkable discovery made over the last decade, which allows researchers to perform very precise edits in genomes. The technology works very broadly across different species (from plants to animals), and although there are a host of details to improve upon, broadly it means we can change any specific “letter” of a genome to another “letter”.
CRISPR is now widely used in basic research and, from its discovery, people realised that it could potentially be used to edit human genomes. One medical use of CRISPR is to edit the cells in a body, for example eye cells or muscle cells, and change those cells to fix a genetic defect. This is in some sense similar to the gene therapy discussions in the 1980s and 1990s. In addition, it is possible to edit embryos at the single cell stage (“the zygote”) to make a genetic change which is present in all cells of an individual.
In developed countries these sorts of procedures are usually regulated as part of In Vitro Fertilization (IVF), where sperm and eggs meet in a dish, and the resulting embryos are placed back into the mother. This procedure can help couples who are unable to conceive naturally.
In addition, in many countries, couples who are carriers of serious genetic diseases can have their embryos genetically screened at an early stage, whilst the embryos are still in a dish. The couples can choose to only have implanted those embryos that do not carry the genetic disease. This is called Pre-Implantation Genetic Diagnosis (PGD). These procedures, with strong national regulation, have been in place since the 1990s and many children have been safely conceived using this method.
The CRISPR approach would add an extra step of introducing CRISPR technology at the first cell stage. This would be followed by screening for a successful edit. Although this is technically possible, there are currently virtually no* serious genetic diseases where pre-implementation diagnosis would not work but CRISPR would.
From what we know about the Chinese example, the researchers aimed to edit a deletion of a specific gene (CCR5) where the deletion is known to be protective of HIV transmission (the families had a HIV positive member so there is a rationale for choosing them). I believe this is a misguided, inappropriate and unethical study. Firstly, there are already entirely appropriate ways to protect children from HIV transmission without changing the genetics. Secondly, we do not know all the consequences of this deletion outside of HIV transmission, though deletions in this gene are relatively common in some populations, so it is clearly compatible with reasonably health human life. Thirdly, such a new procedure should have both ethical and safety considerations broadly discussed. From my perspective, this study failed on all these counts. It is an entirely inappropriate procedure and I believe it would be illegal in all European countries.
It is possible that in the future we will know more about specific genetic combinations and about the safety of using CRISPR in embryos via extensive animal studies. This would allow us to consider how to responsibly use this technology. However, this will require a significant amount of research and new regulations. In the near future, PGD will continue to be a viable option for healthy parents, and many “obvious” uses of genome editing will be better answered via PGD. However, it is worth thinking about sensible regulation before we have to make practical decisions about using CRISPR in embryos.
In a similar way to IVF and PGD technologies in previous decades, society must have confidence in the legislation and regulation around using CRISPR technology. For example, in the UK, the Human Fertilization and Embryo Authority provides regulation enshrined in UK law in this area. Other countries in Europe have analogous legislation and regulation. This allows new technologies, such as mitochondrial donation, to be developed in a way that is medically safe, scientifically and ethically sound, and supported by society.
[*. An explanation of the “virtually no” phrase. There are scenarios where if there are two parents both homozygous for a serious genetic disease and they wish to have children genome editing would be their only option to provide a genome without the defect, similar to PGD. In discussions with practicing clinical geneticists, this precise scenario has not occurred in their practice, but simply by the large number of people in the world, it must occur at some extremely rare rate. However there are other genetic diseases, also very rare but have been observed in my small sample of clinical geneticists, where parents are almost certain to pass on a genetic defect, but are not easy to solve with genome editing, such as balanced translocations. The other scenario where parents could not use PGD was for mitochondrial genetic disease, which is only passed on by the mother and is has a different genetic transmission. This has been tackled by mitochondrial donation, an advanced reproductive assistance technique which went through the HFEA regulation through its research, development and application.]
Read the French version of this post: Les bébés-CRISPR – commentaire scientifique et éthique
Read the German version of this post: CRISPR Babys – Wissenschaft und Ethik auf dem Prüfstand
Read the italian version of this post: Bambini CRISPR – una riflessione scientifica e alcune considerazione etiche.
Read the Spanish translation of this post: Bebés CRISPR – Consideraciones sobre ciencia y ética