For the first time in human history, we not only understand the language of life, but we can also manipulate it. In the past two decades, a lot of advancements have been made to contribute to the realm of genome editing. Genome editing is the combination of techniques that allow us to manipulate the DNA of bacteria, fungi, and even humans. Manipulating genetic codes have an enormous influence and can be used to increase crop yields, produce medicines in bacteria, and even cure genetic diseases.
The Genome Editing 101 series offers to explain the relevant biology of gene editing, the mechanisms by which such techniques work, and the ethical and political problems that arise from this new field of biology. It will be mainly divided into the following chapters:
4. Genome Editing 101: Politics on Genome Editing
5. Genome Editing 101: Ethical Problems in Genome Editing
6. Genome Editing 101: Future of Genome Editing
Gene-editing has been a controversial subject for years, if not decades. This was the case for many technological breakthroughs. People were scared of steam-trains when they first appeared, just like they were of airplanes and computers. There is, however, a large difference between these breakthroughs and the new technology of gene-editing. Nowadays, scientists understand the blueprints of the human body in terms of a single molecule called DNA. Not only is this molecule well-understood, but it can now also be manipulated. As the manipulation of genomes introduces significant ethical questions, this branch of science has been heavily debated in politics too, and the differences between national legislations are astounding. In this article, the United States, China and the European Union are taken a closer look at, on account of these three being the biggest contributors to gene-editing research (Arabi et al., 2022).
The fact that scientists are now able to change the genetic composition of virtually any organism offers great ethical issues. Biological research has been used for political agendas in both the present and the past, from the infamous experiments performed in concentration camps during WWII to the more recent reports on forced DNA extraction and sterilisation of Uyghurs in Xingjiang (Offord, 2019; United Nations, 2022). Now that gene-editing offers new possibilities in biological research, the call for international regulation is becoming louder. That is why, in 2021, the WHO published recommendations on what to refrain from in research (United Nations, 2021).
In this report, the Director General, Tederos, expresses the positive potential of gene-editing techniques such as CRISPR/Cas9 in terms of human diseases. “But the full impact will only be realised if we deploy it for the benefit of all people,” he adds. Most notably, the distinction between somatic and germline gene-editing is stressed in this report. Somatic editing is the manipulation of the cells of one’s body, without any heritable consequences. An example might be a well-defined area occupied by a tumour on one’s skin. In theory, biologists could start therapy to induce mutations in only the cells that make up this tumour. On the contrary, germline editing is when the manipulations are heritable, in other words, it is when an embryo is edited. When this is done, the full embryo that grows into a baby consists only of cells that have been edited, and the same goes for its progeny (Gabel & Moreno, 2019). Given the drastic consequences of germline editing, the WHO is very clear about its regulation: do not commit to it.
CRISPR/Cas9 is known to not be 100% accurate (Listgarten et al., 2018). In other words, it may induce mutations in the genome that were not necessary nor observed. As the consequences of these errors are not yet fully understood, the scientific community is opposed to germline editing, since all of the subject’s cells would possess these errors. Additionally, the ethical concerns are more prominent in this case. Not only are the long-term effects on multiple generations not well understood, but such heritable changes could be used for eugenics (Gabel & Moreno, 2019).
The potential misuse of gene editing, and more specifically germline editing, was exemplified in an infamous experiment conducted by He Jiankui in 2018 in China. Without going into too much detail, it is safe to say that this publication was a shock to the scientific community, as the scientist modified the genome of two embryos in unauthorised research. Only 3 months after this revelation, Chinese policies on gene-editing research have become more restrictive, with much more supervision involved. Punishments consist of fines, ban to commit research, or even criminal charges. Still, clinical researchers in China are worried, as the same regulation now also applies to somatic gene-editing. Although tighter regulations increase the safety of clinical gene-editing, procedures have become significantly more lengthy, which is a hindrance to patients relying on such trials (Normile, 2019).
The policy on gene-editing research in the United States is difficult to describe, primarily because of the different legislations across states. There are some national laws though, and they prohibit clinical trials involving hereditary manipulations of the patients’ genome. Some states do not allow research on human embryos, while others do. The legislation in the European Union is similar to that of the United States. Overall, germline editing is not allowed in the EU. There are, however, national differences, with countries like Belgium and Italy making an exception for this ban if the research has therapeutic or diagnostic implications (Baylis et al., 2020).
The products that are acquired by gene-editing are heavily regulated as well. Because the concept of GMOs, or genetically modified organisms, has existed for a while in the context of agriculture, the legislation in this aspect is much more extensive compared to gene-editing in clinical use. GMOs have been a topic of heavy debate ever since their introduction in the 1990s. The clinical relevance of gene-editing, however, is much younger. Therefore, legislation on this subject is generally less mature and developed (Gabel & Moreno, 2019).
As discussed in the previous article of this series, gene-editing tools, and CRISPR/Cas9 specifically, offer amazing opportunities in the agricultural industry. Theoretically, crops can be engineered to be resistant to chemicals, insects, or droughts. With a growing demand for food and an increasing world population, genetically engineered crops are becoming a more realistic option to solve these problems. However, since this technique is so revolutionary, it is often met with scepticism. The long-term effects are not clear, which makes politicians hesitant to relax regulation (Gabel & Moreno, 2019).
This is perfectly mirrored by a ruling of the Court of Justice of the European Union, which is the EU equivalent of the Supreme Court of Justice of the United States. In 2018, this organisation ruled that genetically engineered crops should fall under the same lengthy and costly procedures as GMOs. This might sound straightforward, but in fact it has caused much criticism by experts, claiming that genetically engineered crops are intrinsically different from gene-editing or other GMOs (Stokstad, 2018).
In the past, genes from other species were inserted into crops. An example of such engineered plants is the Bacillus thuringiensis (Bt) crops. These are crops that have an inserted gene originating from the bacteria B. thuringiensis. Such organisms, into which a foreign gene has been knocked-in, are referred to as transgenic organisms. These Bt crops produce a toxin that kills insects when they feast on these crops, but is known to not be harmful to humans. These crops are the classical example of GMOs (Abbas, 2018).
What makes new genomic techniques (NGT), such as CRISPR/Cas9, different from engineered crops is the origin of the induced genetic elements. New tools, such as CRISPR/Cas9, can very efficiently and precisely change a small or large amount of nucleotides. Rather than introducing a completely new gene and creating a transgenic crop, mutations are introduced that could theoretically occur in nature through evolution. This is the main difference between the classic GMOs and organisms treated with new gene-editing tools. The genetic composition of the former would simply not occur in nature, while that of the latter ones would (Stokstad, 2013).
Because of this distinction, many experts feel it is unfair to make genetically-engineered crops go through such a lengthy and costly process that can take many years to complete. At the time, Sarah Schmidt, affiliated with the Heinrich-Heine Universität of Dusseldorf, said that this ruling forces companies to go through a process costing about 35 million dollars per crop (Stokstad, 2013). John van der Oost, one of the scientists that contributed to the finding of CRISPR/Cas9, fears the occurrence of monopolies, as this means that small companies, nonprofits, or universities will not be able to bring genetically-engineered crops to the market (Pothering, 2019).
Van der Oost has been very critical of politics concerning gene-editing ever since. In an interview with AgFunderNews in 2019, he expressed his frustration: “People who don’t have the proper scientific backgrounds cannot judge how safe this is or how far we want to take this. If they have to vote on it, they say ‘We don’t know what this is, so we don’t trust it.” (Pothering, 2019) Frustratingly, other countries have ruled very differently. The Department of Agriculture in the United States ruled that it would regulate plants that could have been given rise to by traditional breeding techniques different from GMOs. Additionally, in China, there is much more room for the development of such crops (Mallapaty, 2022). As a result, Van der Oost fears that researchers and companies in Europe will fall behind and become unable to compete with much faster research elsewhere.
Looking at the clinical applications of CRISPR/Cas9, a similar trend is visible. The current legislation in the EU remains unclear, as new policy should be decided on in the near future (Anliker et al., 2022). In the meantime, the number of clinical trials with gene-editing tools in the US and China is rising. Interestingly though, institutions in Europe are sometimes involved in such studies conducted overseas, so the experience is there. A paper published in 2022 shows how dominating the US and China are in clinical trials conducted with gene-editing tools, by analysing the content and country of publications with respect to gene-editing in the clinic (Arabi et al., 2022).
It seems, however, that change in the EU is inevitable. Politico, a (digital) newspaper that reports on US and international politics, published an article in October 2022 titled “Like it or not, gene-edited crops are coming to the EU”. In this article, influential people are said to have changed their minds on current EU policies concerning genetically-engineered crops. Climate change is mentioned as one of the major causes. Obviously, with more unpredictable and extreme weather conditions on the horizon, it would seem logical to allow the production of crops that are more resistant to these conditions. To that end, Spain’s Minister of Agriculture, Luis Planas, expressed his enthusiasm about crops that require less water or fertilisers in a meeting for all Agriculture ministers of the EU. Additionally, it seems that the food insecurity caused by the war in Ukraine rises as another strong reason for changing views on this policy (Brzezinski, 2022).
To conclude, the research and legislation of gene-editing are still in their early stages. As research continues to grow, both the science and politics in this field will become more developed in the future. It is, however, worrying that countries vary significantly in such legislation, and no international organisation is established to monitor national policies. The fact that the European Union is supposedly changing its view on conservative policies concerning crops treated with NGT is promising, and stronger European contributions to the field can be foreseen. Nonetheless, the number of ethical questions raised by the development of these tools will likely increase. This will be the topic of the next article in this series.
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Anliker, B., Childs, L., Rau, J., Renner, M., Schüle, S., Schuessler-Lenz, M., & Sebe, A. (2022). Regulatory considerations for clinical trial applications with CRISPR-based medicinal products. The CRISPR Journal, 5(3), 364–376. https://doi.org/10.1089/crispr.2021.0148
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Cover image: Denayunevz. (n.d.). Political Candidate Hand Drawn Illustration with Debates Concept for Promotion Election Campaign, Active Discussion and Get Votes. [image]. https://www.vecteezy.com/vector-art/9951839-political-candidate-cartoon-hand-drawn-illustration-with-debates-concept-for-promotion-election-campaign-active-discussion-and-get-votes
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Figure 7: Arabi, F., Mansouri, V., & Ahmadbeigi, N. (2022). Gene therapy clinical trials, where do we go? An overview. Biomedicine & Pharmacotherapy, 153, 113324. [image]. https://doi.org/10.1016/j.biopha.2022.113324