by Vivien Doszpot-Szútor
One of the latest technologies with unknown effects is gene editing with the CRISPR process, the use of which can determine the genetic stock of humanity and its environment in the future to an unprecedented extent. Although this gene editing method also affects the modification of DNA, it does not result in a GMO product. In terms of the legal regulation of the area, this distinction is far from clear and there is a difference between US and European Union regulations. While the US regulation focuses on the simplest possible authorization procedure, the EU regulation follows the precautionary principle for the CRISPR gene editing process as well.
Since the 1970s, researchers have been able to modify DNA. There were early attempts to heal with genetic technology, but these failed,[i] so the scientists declared a moratorium and did not want to use the gene editing method on humans until it became safe.[ii] In 1997, the Council of Europe issued the Oviedo Convention, according to which the ratifying states prohibit all attempts or procedures to modify human DNA (except for preventive, diagnostic or therapeutic purposes, in the case that this does not aim to modify the genome of the descendants).[iii] However, while genetic engineering on humans has been banned in a large part of the world, the market for genetically modified plants and animals for human consumption is thriving. In the United States of America, various genetically modified products (GMOs) suitable for human consumption, such as corn or salmon, are being approved one after the other.[iv] However, the long-term effects of human or animal consumption of GMOs are not yet known, since the first GMOs were put on the market in 1994.
In 2012, the research team of Jennifer A. Doudna and Emmannuella Charpentier created the newest method of gene editing, the CRISPR process,[v] with which they turned the world of genetic technology upside down. The procedure is cheaper and faster than previous recombinant DNA technologies,[vi] and the equipment required for the method can be found in most scientific and commercial laboratories.[vii] As long as there was a moratorium on the human application of previous genetic engineering procedures, this ban does not apply to the CRISPR method. In 2015, it was first used on non-viable embryos, and in 2018, Chinese researchers used this method to cure twin girls who were still in the fetal stage at the time. The Chinese researchers were condemned by the world's scientific community for using an experimental method on unborn children that would have achieved the same results with traditional medical methods. They also had to answer for their actions in court and in December 2019, the Nanshan District People's Court in Shenzhen found the researchers guilty, among other things, for carrying out their healing activities without a license and thus violating Article 336 of the Criminal Law of the People's Republic of China.[viii]
CRISPR is expected to be most useful in the treatment of genetic diseases that are monogenic – that is, caused by a single mutant gene.[ix] However, the technology is intended to be used not only in medicine, it can be used in many ways. It can help us in reviving already extinct species, in the creation of new species, and even in the extermination of species, such as the mosquito population that spreads many diseases. In the same way, it can be used for xenotransplantation if, for example, it is possible to grow an organ similar to a human in a pig. Furthermore, it can also be used in agriculture in the same way as GMO.[x]
Since the release of the procedure in 2012, we have already reached CRISPR 3.0. The essence of the CRISPR 1.0 method was that it actually cut the DNA, the cells repaired this cut and thereby eliminated the faulty gene mutations (at that time the procedure was called gene editing scissors). CRISPR 2.0 acts on the four bases of DNA (A, C, G and T) and is able to convert them from one to another. ’It’s no longer acting like scissors, but more like a pencil and eraser,’[xi] says Kiran Musunuru the cofounder of Verve Therapeutics. And CRISPR 3.0 makes it possible for researchers to exchange pieces of DNA and insert new pieces of genetic code into the chain. The latter method is currently only tested on animals in laboratories, but scientists expect that it will be able to cure even more genetically inherited disorders.[xii]
Researchers distinguish between GMOs and products modified with CRISPR technology. While the genetic modification in the product produced by GMO requires DNA from another species (transgenic) or from another individual of the same species (cisgenic), with the CRISPR method, one's own DNA can be subjected to the modification without the need for foreign genetic information.[xiii] Precisely for this reason, researchers consider gene editing with CRISPR to be a safer method than previous genetic engineering procedures that produce GMO products. However, it is up to consumers[xiv] and legislators whether they too consider one method safer than the other and whether they distinguish between the use or regulation of the two methods. In terms of regulation, the legislation of the United States of America and the European Union are also divided in this regard.
In the United States of America, there is a lengthy procedure for the authorization of GMOs, which, due to its costly nature, forces smaller companies out of the competition, which is why the market is monopolized in many cases.[xv] GMOs are approved by three organizations in the US: the FDA, the EPA and the USDA. However, in order to license plants produced with CRISPR gene editing technology, only the FDA's permission is required, neither the USDA nor the EPA has a say in the decision, because the edited DNA does not contain new genetic code. So, neither the environmental protection nor the supreme agricultural office decides on the use or application of the plant produced with CRISPR in the US. This may mean that, due to the difference in technologies, CRISPR poses less of a threat to the environment and health than GMO, but it may also mean that they hope for much more benefit from the former procedure, so it is important that the administration will be smooth and that they can enter even smaller companies to the market. However, we also have to see that one of the creators of the procedure, Jennifer A. Doudna, warns us that ’we also need to understand the risks of gene editing. Because this method gives us the opportunity to radically and irreversibly change the biosphere.’[xvi] The experts also add that if consumers will compare the product produced with CRISPR to the GMO product, it will not be possible to use the full market potential inherent in CRISPR in the long term.[xvii] By the way, the European Union solved the issue of regulation very simply and brought all genetically modified plants and animals under the scope of the GMO directives.[xviii] Although the legislation of the European Union does not cover genetic engineering applied to humans, after most of the EU states ratified the Ovideo Convention created by the Council of Europe, it can be said that this problem has also been resolved. The EU is likely to apply the precautionary principle for this unknown technology, since objectively there is a risk that if a plant, animal, and later a human being that has undergone the CRISPR process gets outside the walls of the laboratory, more damage will be caused than the benefits scientists hope for. At the same time, on the part of the legislator, classifying as GMO a product that is not GMO according to the current state of science is an interesting decision. Although with this step a clear position can be conveyed to consumers, the question is whether they will be able to maintain this opinion even if the CRISPR process will indeed be able to heal diseases of genetic origin that could not be healed by other methods until now.
In the case of genetic engineering procedures, the main question is always how far we can go? Is it ethical to modify the genome of an unborn fetus? Do we have the right to use gene editing that will be preserved in the generations that follow us? Aren't we causing even more damage to our environment by genetically editing our animals, plants, and thus our food? The biggest problem with these questions is that we don't know the answers for the time being, and it is expected that it will only become clear later in the medium to long term whether or not we have done the right thing. The problem with regard to genetic engineering is that there is no consistent international regulation that every nation feels is their own (because while the CRISPR technology that can be used on humans is in the clinical research phase in the US, the EU does not have its own legislation for such a case), this is why a genetic technology competition will develop in which no one will want to be left behind.
Jennifer A. Doudna rightly asks, ’Are we, as a species, ready to take control of—and take responsibility for—our evolution through purposeful gene pool modification, rather than random mutations?’[xix] I can only hope that an international consensus-based, legally binding answer to this question will come before researchers start playing with human DNA in such a way that the change will also be found in the genome of the future generation. However, the international perception of the issue is complicated by the contrast between the US and the EU regarding the issue of genetic engineering using the CRISPR method. As long as this unknown technology is easily permitted by one state and banned by the other as a GMO, a competition will develop in which it will not be possible to know whether the parties are not overstepping moral limits in the heat of the competition. The question is, will CRISPR be the bright shining star of genetic engineering, or will the duality of legal regulation extinguish its light and enter the shadow of GMO?
[i] For example Jesse Gelsinger’s case in 1999.
[ii] Famous Asilomar’s conferences
[iii] Council of Europe: Convention for the protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (ETS No. 164) Article 13 – Interventions on the human genome: ’An intervention seeking to modify the human genome may only be undertaken for preventive, diagnostic or therapeutic purposes and only if its aim is not to introduce any modification in the genome of any descendants.’ https://rm.coe.int/168007cf98
[iv] First GMO products hit the US’s market in 1994, it was a GMO tomatoes. The first GMO’s salmon hit the market was in 2015.
[v] CRISPR – Clustered Randomly Interspersed Short Palindromic Repeats
[vi] Recombinant DNA technology – ’is the joining together of DNA molecules from two different species. The recombined DNA molecule is inserted into a host organism to produce new genetic combinations that are of value to science, medicine, agriculture, and industry.’ Anthony J. F. Griffiths: recombinant DNA – genetic engineering https://www.britannica.com/science/recombinant-DNA-technology
[vii] Alberto Asquer – Michael Morrison: Editorial: Regulation and governance of gene editing technologies (CRISPR, etc.) https://www.frontiersin.org/articles/10.3389/fpos.2022.1027410/full
[viii] Asquer – Morrison
[ix] Jennifer A. Doudna: Crack in Creation, Vintage Publishing, 2018. 206.
[x] Doudna 184-187.
[xi] Jessica Hamzelou: Next up for CRISPR: Gene editing for the masses? January 19, 2023 https://www.technologyreview.com/2023/01/19/1067074/next-for-crispr/amp/
[xii] Hamzelou
[xiii] Aaron M. Shew – L. Lanier Nalley – Heather A. Snell – Rodolfo M. Nayga Jr. – Bruce L. Dixon: CRISPR versus GMOs: Public acceptance and valuation, 9 November, 2018. https://www.sciencedirect.com/science/article/pii/S2211912418300877
[xiv] ’A survey by the Pew Research center found that 57% of Americans believe that it is “generally unsafe to eat GMO foods.”’ Hailey Barneich: CRISPR and GMO: the Unlikely Hero for the World, Febr 20, 2021. https://pha.berkeley.edu/2021/02/20/crispr-and-gmo-the-unlikely-hero-for-the-world/
[xv] Doudna 167.
[xvi] Doudna 157.
[xvii] Shew – Nalley – Snell – Nayga Jr. – Dixon
[xviii] Directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms, Regulation 1829/2003 on genetically modified food and feed and Regulation 503/2013 on applications for authorisation of genetically modified food and feed
[xix] Doudna 205.
