Europe Faces CRISPR People
The evolving European regulatory landscape for gene-editing in humans
The world of biotechnology was transformed by the discovery of the CRISPR-Cas9 gene editing technique by Jennifer Doudna and Emmanuelle Charpentier ten years ago. CRISPR enables cheaper and more precise genetic modifications than ever before. The European Commission has hailed CRISPR’s potential in the area of agriculture as a way of creating more environmentally resilient, disease-resistant, productive and/or pesticide-free crops. CRISPR also has potential environmental, industrial, and medicinal applications, such as the development of plastic-destroying bacteria, biofuels, and medicines.
No doubt the most controversial potential use of CRISPR is gene-editing in humans. The European Parliamentary Research Service (EPRS), a sort of in-house think-tank serving EU legislators, has published an excellent study by legal scholar Ana Nordberg and policy analyst Luisa Antunes on the topic, detailing the current state of regulation and debate in Europe. The following overview is largely derived from that paper.
The two basic applications of CRISPR in humans are somatic interventions that treat an ailment by targeting non-reproductive cells and germline interventions (either of an embryo or of gametes or gonads) that can potentially be passed on to future generations.
Through somatic edits, CRISPR could potentially treat many cancers, and is already being used to successfully treat certain forms of blindness and sickle-cell anemia, a disease which otherwise radically reduces life expectancy. For somatic treatments, which might take the form of an injection into the blood stream or a targeted organ, standard medical and pharmaceutical laws typically apply.
The EPRS study notes: “Although EU pharmaceutical legislation is comprehensive, experts argue that there is a risk that some genome editing therapeutic products can never be tested in a clinical trial.” This is because EU regulation on clinical trials, updated in 2022, stipulates that “[n]o gene therapy trials may be carried out which result in modifications to the subject's germline genetic identity.” This makes it impossible to conduct trials affecting gonads, such as testicular cancer treatment.
Germline interventions insert permanent, transmissible genetic changes. The most immediate possible application is the prevention and eradication of often crippling monogenic disorders – that is, being caused by a single gene – such as cystic fibrosis, Huntington’s disease, and Duchenne muscular dystrophy. However, CRISPR could also be used for more complex germline therapies or for outright human enhancement, such as boosting of intelligence.
Between anti-eugenics and therapeutics: European texts on germline modification
Discussion of germline interventions are haunted by the shadow of eugenics and a sense that the existing human gene pool is inviolable, while at the same time not wishing to ban obviously beneficial treatments that require gene editing. This is reflected in the ambiguity of many European texts governing gene editing.
For example, the Council of Europe’s 1982 Recommendation on Genetic Engineering states that “the rights to life and to human dignity protected by Articles 2 and 3 of the European Convention on Human Rights imply the right to inherit a genetic pattern which has not been artificially changed.” At the same time, the Recommendation asserts that this right “must not impede development of the therapeutic applications of genetic engineering (gene therapy), which holds great promise for the treatment and eradication of certain diseases which are genetically transmitted.”
Similarly, the 1997 Oviedo Convention on Biomedicine, ratified by many European states, stipulates:
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 (Article 13, Oviedo Convention).
This would seem to ban germline editing outright. However, the EPRS study notes that this wording is in fact ambiguous: legal scholars argue that germline editing is allowed if this not the goal in itself, but only the means to preventing or treating a disease.
The EU Charter of Fundamental Rights – which applies to the EU institutions and to national governments when applying EU law – affirms persons’ rights to their physical and mental integrity, and under this heading affirms “the prohibition of eugenic practices, in particular those aiming at the selection of persons.” This apparent blanket ban is qualified however the absence of an agreed definition of eugenics. As the EPRS study notes:
It is debatable if and to what extent can the concept of eugenics cover free and informed individual choices; if it is only meant as government sponsored programs or if it addresses also private entities such as employers. It is also a matter for debate what type of interventions and treatments (or conjugations thereof) might be qualified as eugenic practices. The CJEU [Court of the Justice of the European] in Netherlands v European Parliament and Council (Case C-377/98, at grounds 70 and 78 to 80) made a narrow interpretation of eugenics, as equivalent to practices aiming at the selection of persons and linking it to the concept of crimes against humanity (Article 7(1) (g), Statute of the International Criminal Court). Examples provided refer to “campaigns for sterilisation, forced pregnancy, compulsory ethnic marriage,” supporting a reading that Article 3 of the EU Charter only applies to public authorities and to widespread or systematic practices.
Practices such as women selecting sperm from a highly-educated and healthy donor, or aborting a fetus with a severe congenital disability, would under this narrow definition not count as “eugenics” and as such are not banned.
National legislation: a varied but mostly bio-conservative landscape
Relevant legislation on germline gene therapies in the EU are essentially national and variable. As the study notes: “The current legal framework governing human genome editing is complex, fragmented and diverse.” Germany, for obvious historical reasons, has extremely restrictive legislation justified on grounds of human dignity. Even basic research on modified gametes is banned and stem cell research is virtually banned (this is far stricter than U.S. President George Bush’s Christian-influenced ban on stem cell research, for this only applied to federal funding).
In Italy, strict anti-editing legislation, justified on anti-eugenic grounds, has been attacked in the courts for undermining disease prevention. EPRS:
The controversial 2004 Act on Medically Assisted Reproduction bans any form of eugenic selection of embryos and gametes, or interventions which, by means of selection, manipulation or artificial manipulation, are intended to alter the genetic heritage of the embryo or the gametes or to predetermine their genetic characteristics, with the exception of the interventions for diagnostic and therapeutic purposes (Article 13(3)(b), Act N.40/2004).
The Constitutional Court declared in 2015 this provision partly unconstitutional insofar as it encompasses a prohibition of embryo selection in order to avoid implantation of embryos carrying severe genetic transmissible diseases (Italian Constitutional Court, decision of 18/11/2015).
Great Britain, while having banned clinical germline editing, is the first country to allow mitochondrial replacement therapy. Under this procedure, the mother’s unhealthy mitochondria is replaced by a donor’s, thus resulting with a child with 99.9% the couple’s DNA and 0.1% the donor’s. As EPRS notes, (re)definition of terms and (re)categorization of the procedure were crucial to its acceptability:
In strict legal terms, the technology entails a modification in germ cells transmittable to future generations, by inserting healthy donor genetic material. However, the UK parliamentary and public debates carefully avoided the use of the terminology genome editing, manipulation, modification or similar. Discussions focused mostly on weighting the potential medical risks of using a new assisted reproduction technique against potential benefits of avoiding pain, suffering and loss of life associated with severe diseases.
Therapeutic germline therapy seems in reproductive contexts to be permissible in Portugal and Spain. Belgium for its part has among the most permissive legislation:
Everything that is not prohibited by the law is allowed. The conclusion, supported by the parliamentary debate, is that germline genome editing is permitted for corrective purposes (meaning elimination or correction of genetic diseases), if approval of the local ethics committee and the Federal Commission on scientific research on embryos in vitro is obtained.
It is notable that little Belgium more generally is something of a biotech powerhouse, representing 3.4% of EU GDP but 16% of Europe’s biotech turnover.
Debate beyond the toxicity treadmill
“Eugenic” germline interventions or enhancement, that is those interventions aiming at “selection or improvement of nonpathological characteristics of the human species,” seem to be banned in all national jurisdictions in the EU with relevant legislation. This seems justified today insofar as CRISPR gene-editing’s safety and precision in humans is still unclear and can no doubt be improved. Germline gene-editing should initially be restricted to therapeutic interventions against monogenic diseases where the known harms and risks of the disease, often devastating or fatal, seem greater than the unknown risks of CRISPR.
It is striking that many of top (bio)ethical thinkers have endorsed some form of moral duty towards the genetic well-being and improvement of future generations. As Nordberg and Antunes note:
[John] Rawls, although declining to discuss eugenics, asserts that parents will want to ensure their offspring have the best genetic endowment (Rawls, 1999) arguing that by reason of the difference principle – unequal distribution is acceptable if it is to the advantage of those who are worst-off (Rawls, 1999 and 2001) – “greater abilities are a social asset to be used for the common advantage” (Rawls, 1999) and therefore society should take measures to at least “preserve the general level of natural abilities and to prevent the diffusion of serious defect” (Rawls, 1999).
Along a similar line of reasoning, [Allen] Buchanan and co-authors postulate that genetic enhancements are morally acceptable and commendable, and interventions to prevent disabilities a moral imperative (Buchanan et al 2000). [Ronald] Dworkin goes further, stating that morality requires society to allow parents to genetically enhance their children to afford them broader life choices and changes of success. (Dworkin, 2000). These arguments endorse all genetic interventions – heritable or not – provided that these have a beneficial purpose or provide an advantage, but still require a legal predetermination of what can be characterised as such.
The contrast with most European conventions and laws on these issues is quite striking.
It should be noted that there are also intellectual heavyweights opposing genetic enhancement, not least Jürgen Habermas, Michael Sandel, and Francis Fukuyama. Others, like the Australian philosopher Julian Savulescu, emphatically argue that there is a moral duty for enhancement on grounds of the principle of procreative beneficence, that we have a duty to ensure our children as created in the best conditions and with the best endowment possible.
Nordberg and Antunes stress the complex of principles involved on enhancement: “Any regulatory or governance activity anchored in a prohibition of nontherapeutic genome editing would have to carefully address the complex and delicate interface with the right to health, right to benefit from science and personal autonomy over one's body.”
The authors ultimately argue that the very terminology used may be unhelpful to legislative debate: “The use of ‘human enhancement’ as a criterion for unacceptable interventions is not useful, as it is too vague, value-charged and difficult to enforce.”
A “toxicity treadmill” seems to be at work whereby certain words become so loaded and so contested in their very definitions as to make them unhelpful for clear and dispassionate debate. As such, certain bioethical authorities are increasingly questioning the usefulness of distinctions like “therapy/enhancement” in favor of discussing interventions on a case-by-case basis.
Quo vadis Europa?
National regulation of gene editing will to some extent be ineffective in the absence of international standards. Germany’s ban on research involving embryos seeks to overcome this through extraterritorial applications: German-based scientists can be sanctioned for international research collaboration involving embryos. Even such harsh national measures are unlikely to be very effective: repressive jurisdictions will simply see research, business, and treatments, both somatic and germline, emerge elsewhere.
This has already occurred with agricultural biotechnology because of the near-impossibility of marketing traditional genetically-modified foods in the EU. As a result, European agricultural biotech is virtually nonexistent, while being a thriving sector in the United States, Brazil, Argentina, Canada, and India. Since Brexit, the United Kingdom has moved to lift EU-inherited rules to foster research gene-edited crops.
The stakes in gene editing in humans – with their potential both for misuse and for treating or exterminating numerous genetic diseases – are even higher. Europe’s diverse national regulatory landscapes means that at least some countries will engage strongly in this movement. With European biotech booming in recent years, notably since the COVID crisis, Europe has the potential to be at the forefront of research and treatments fighting some of the worst genetic diseases afflicting humanity.