Abstract
In general, to modify the human germline is prohibited. However, regulating the use of HHGE might be a more efficient method than the actual ban. Indeed, when genome editing is safe for introduction in clinical practices, it is frequently proposed that the prohibition is lifted solely for therapeutic purposes, i.e., to eliminate serious genetic diseases. Definitions of the concepts of health and disease are controversial and may only be reached by adopting a value-laden approach, which may rise concerns about legal certainty and have possible discriminatory effects. Nor the threshold of the seriousness of the disease might be used to solve these issues. A different model might then be adopted for the assessment of the permissibility of HHGE, i.e., the PGD model. However, such model should not be implemented as the only criterion, but should rather be a “minimum threshold”: HHGE should be allowed whenever used to correct a genetic defect for which PGD is possible.
1 Introduction
The history of human development is characterised by man’s desire to improve and somehow gain control over their human biological destiny.1 The field of human genome editing is no exception in this respect. Indeed, since the discovery of DNA, the scientific community has been focusing on trying to achieve the capacity to make targeted changes to the human genome, particularly in order to cure genetic diseases. The development of systems like ZFNs, TALENs and especially CRISPR-Cas9 family of genome-editing tools, often referred to as “the Breakthrough to Genome Editing,”2 has brought us closer to this aim by making it possible to perform genome modifications in a precise, efficient, and cost-effective way.3 These are exceptional tools for achieving great therapeutic purposes, but at the same time they raise issues related to the social consequences and the ethical permissibility of their use.
This is particularly the case for heritable human genome editing (HHGE), i.e., when changes are made to germline cells, and thus to the genetic material of eggs, sperm or any germ cells, including the cells of early embryos.4 The genetically modified embryo is then transferred to a uterus in order to initiate a pregnancy and give birth to a child with a modified genome. Unlike modifications made to somatic cells, which are all other cells in the human body, alterations of the germline cells are then inherited by the descendants of the modified person,5 a peculiarity that raises fervent hope for future therapeutic treatments, but also great societal, ethical and legal concerns.6
Indeed, in general terms, HHGE may be used to alter the human genome at least for the following aims: (1) the prevention or treatment of genetic disorders (therapeutic purpose), and (2) the optimisation of certain traits or abilities, and more broadly the attempt to modify desired traits in offspring that are not directly related to a disease (enhancement).7 However, the dividing line between these different purposes is far from being clear. Even though it is unrealistic to think that we will ever be able to alter complex human traits such as strength or intelligence, mainly because of their multifactorial and extremely complex nature,8 interventions in the human genome such as increasing athletic performance by altering the erythropoietin receptor gene or ensuring disease resistance may not always be considered medically necessary. Consequently, modifications of this kind might still qualify as enhancement and thus raise enormous concerns related to, among the others, the protection of the human genome, possible violations of the right to self-determination of the future person, and of human dignity.9
For these reasons, and because of the unsolved societal, ethical, legal, and technical issues,10 the HHGE is sometimes referred to as “a red line that should never be crossed.”11 Currently, this restrictive approach is reflected in the European and International legal instruments applicable to HHGE, as well as that of the vast majority of the countries, that mainly prohibit the use of HHGE for reproductive purposes.12 However, in recent years international scholars’ and institutions’ opinion on the matter started to increasingly ask for the establishment of a responsible and prudent pathway to an effective regulation on the matter. Indeed, nowadays the main question appears to be less whether HHGE should be pursued and more how and under which circumstances.13 In this regard, it is frequently suggested to use the therapeutic purpose as a threshold for the permissibility of HHGE and as one of the guidance principles for a regulatory pathway on the matter, especially in its meanings of “correction of serious (monogenic) diseases” or “restoration of health.” However, there is no consensus on the definition of these terms.
Therefore, after an overview of the current legal framework applicable to HHGE and a brief analysis of the shift in public perspective over a call for a responsible pathway in Section 2, in Section 3 I argue that the distinction between “therapy” and “enhancement” is still somehow valuable in itself for the purpose of assessing the permissibility of HHGE and that at least two opposite approaches may be adopted to define the concepts of disease and health on which that distinction relies: naturalism (value-free) and normativism (value-laden). While the first approach might be preferrable, value-free definitions of these concepts appear difficult to be reached. Therefore, only a value-laden approach seems feasible, which however raises concerns in terms of legal certainty and possible discriminations. Neither it appears feasible to adopt a value-free definition of the threshold of the seriousness of the disease, with the aim of reducing the discretion on decisions about the permissibility of HHGE.
Then, in Section 4 I analyse an alternative method to discern between permissible and unlawful use of HHGE: the so called preimplantation genetic diagnosis (PGD) model, i.e., to adopt the same thresholds used to assess whether PGD might be undergone in a given case.14 PGD is a procedure used to examine cells from oocytes or in vitro fertilized embryos to detect genetic alteration responsible for possible genetic diseases and thus enable prospective parents to choose to implant only “healthy” embryos.15 I argue that because of the differences between PGD and HHGE it may be problematic to adopt exclusively the PGD model to assess the permissibility of HHGE. On the contrary, such model might be used as a complementary one, meaning that HHGE might be allowed at least for preventing the occurrence of any of the genetic diseases for which PGD is already permissible.
As an introductory and general remark, the whole analysis starts from the assumption that at some point in the future the use of HHGE for reproductive purposes will be found safe and effective enough for standard clinical application.16 However, like any other medical intervention, HHGE for reproductive purposes will always entail an unavoidable degree of risk and possible side effects. Therefore, as a general criterion, HHGE may be said to be safe and effective when the benefit/risk ratio of their use is deemed appropriate under scientific terms for clinical application.
2 The Framework Applicable to HHGE
2.1 Legal Instruments Applicable to HHGE
At the International level, the Universal Declaration on Human Genome and Human Rights forms “the basis of ‘soft law’ in the area of human genome governance,”17 with the aim of preserving the human genome from improper manipulations.18 Illustrative of this goal is Article 1, which qualifies the human genome as “the heritage of humanity” in a symbolic sense. Even though the Declaration recognises the importance of research on the human genome and the resulting applications, in the Preamble it is emphasized that “such research should fully respect human dignity, freedom and human rights.” Therefore, Article 11 prohibits the performance of practices which are contrary to human dignity, among which Article 24 includes germ-line interventions.19 However, these instruments made no reference to the purpose of HHGE as a criterion for assessing its permissibility.
At the regional level, already in 1997 the so called Oviedo Convention, the first multilateral treaty and regional binding legal instrument in the field of biomedical law,20 established in Article 13 what is considered to be a ban on HHGE for reproductive purposes, with no distinction between therapeutic aims and enhancement, and at the same time it recognises the legitimacy of therapeutic somatic interventions.21 Reasons for such approach may be found in the Oviedo Convention’s Explanatory report, where it is stated that HHGE “may endanger the individual and the species itself” and that “the ultimate fear is of intentional modification of the human genome so as to produce individuals or entire groups endowed with particular characteristics and required qualities.”22
Moreover, a more permissible approach is adopted in some European soft law instruments. Indeed, Recommendation 934 on genetic engineering explicitly states that the right to inherit a genetic pattern not artificially modified23 “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,”24 thus suggesting that in principle therapeutic applications of HHGE do not violate such right. In this regard, this Recommendation further asks for “the boundaries of legitimate therapeutic application of genetic engineering techniques [to] be clearly drawn” and calls for regulations on the protection of “individuals against non-therapeutic applications of these techniques.”25 Along the same line, in 2017 Recommendation 2115 recognises that HHGE raises “complex ethical and human rights questions, including — but not limited to — unintended harm which may result from the techniques used, access and consent to such techniques, and their potential abuse for enhancement or eugenic purposes.”26
At the national level, the legal approaches adopted by different legislators vary greatly. By way of example, and by no means attempting to be exhaustive,27 some Member States prohibit the use of HHGE for whatever purpose, such as Germany,28 while others permit their use exclusively when the aim is therapeutic. For instance, Italy prohibits the selection of embryos for eugenic purposes, by selecting, manipulating, or using other artificial technical measures, whose aim is to modify the genetic heritage of the embryo or predetermine its genetic characteristics.29 By way of exception, however, interventions for therapeutic or diagnostic purposes are allowed, when used to safeguard the health and development of the embryo itself, and if there are no alternatives available.30 Furthermore, some legislations impose a general ban on HHGE while at the same time allowing to conduct research in that regard if the aim is therapeutic. Indeed, the French Civil Code establishes both a prohibition to intervene in the genetic characteristics of a person so as to also modify its descendants, and an exception in this regard for research when aimed at the prevention, diagnosis, or treatment of diseases.31 An analogous categorical ban is in force in Greece.32
2.2 Scholars’ and Institutions’ Approach to HHGE — The Call for an Effective Regulation
In the first major round in the debate surrounding HHGE, when these technologies still had a high rate of side effects and inaccuracies,33 international scholars, institutions and legal experts were almost unanimously in favour of an international ban for both research and clinical use, without making any distinction between therapeutic purpose and enhancement.34 While recognizing the tremendous potential of these techniques,35 the fear that HHGE could violate fundamental human rights and challenge existing values prevailed over the possible (therapeutic) benefits,36 and the adoption of a restrictive approach on the matter was perceived as the best suitable solution to protect the different rights and interests at stake.
However, this restrictive approach came soon under pressure. Indeed, first in 2016 UK licensed a research project on HHGE,37 and then in 2015 and 2019 both UK38 and Greece39 granted permissions to clinically use mitochondrial replacement technique (MRT), a technique which results in modifications of the germline that can be inherited.40 MRT is an in vitro fertilization technique used to replace a woman’s pathogenic mitochondrial DNA (mtDNA) with the one of an healthy donor, thus preventing the transmission of serious mitochondrial DNA-based diseases.41 These scientific developments were perceived as first cracks in the existing legal framework in the field.42 Moreover, in November 2018 the controversial experiment of the Chinese researched He Jiankui led for the first time to the birth of twin girls whose genomes had been edited at the embryonic stage with the aim to confer them resistance to HIV infection.43
Eventually, through time scholars started to question the prohibitive approach on HHGE thus far adopted,44 and to call for the establishment of a responsible and prudent pathway to an effective regulation on the matter, labelled as “more realistic and effective than a prohibitive model.”45 Illustrative examples of this change in trend are the 2017 Report issued by the National Academy of Sciences and the final statement of the Second International Summit held in Hong Kong, where Dr. He presented his experiment. On the one hand, the former, often referred to as “the game changer,”46 enshrines a fundamental permission on HHGE guided by formal and material criteria, as long as the risks associated with its use could be addressed more reliably.47 On the other hand, in its final statement, the organizing committee reaffirmed that “the scientific understanding and technical requirements for clinical practice remain too uncertain and the risks too great to permit clinical trials of germline editing at this time.”48 However, at the same time, it was stated that scientific progresses in the field suggested that “it is time to define a rigorous, responsible translational pathway,” because “germline genome editing could become acceptable in the future” if the risks associated with these techniques are addressed and certain criteria are met, which include the existence of “a compelling medical need.”49
Even though there are international scholars and institutions still in favour of a general ban on HHGE, whatever the purpose,50 the request for an effective regulation on the matter may be said to have started to emerge.
3 The Therapeutic Purpose Threshold
Traditionally, the debate on the ethical and legal legitimacy of HHGE pivoted around the distinction between its use for therapeutic purposes and that for enhancement.51 However, in recent years, this approach has been challenged, especially by those who believe that such distinction should be abandoned altogether52 or replaced by the principle of the best interest of the (future) child.53
I believe that the therapy/enhancement distinction is still a relevant one in the debate on the permissibility of HHGE.54 Indeed, as demonstrated in Section 2, scholars and international institutions calling for a regulation on HHGE frequently refer to the therapeutic purpose as the theoretical threshold for assessing the permissibility of HHGE and one of the guidance principles for a regulatory pathway on the matter.55 Such purpose is then often translated into the prevention or cure of serious genetic diseases. For instance, the 2017 report of the National Academy of Sciences expressly suggested in Recommendation 5.1 to include “the prevention of serious diseases” among the criteria to guide the permissibility of HHGE, and the National Academy of Sciences in 2020 proposed that at least at the beginning “1) the use of HHGE [should be] limited to serious monogenic diseases,” defined as one that causes severe morbidity or premature death.56 The distinction between therapy and enhancement is also mentioned as a relevant one in those previous or recent opinions calling for a moratorium on HHGE.57 Furthermore, such dichotomy is also embedded in regulations and public opinions on biomedical technologies which raise concerns similar to those related to HHGE (e.g., PGD, as explained further in Section 4). Finally, consensus among scholars is almost unanimous in recognising that if HHGE technologies are to be allowed in the future, it will be for therapeutic purposes, and specifically for the “treatment of serious genetic disease,” at least at first.58
For all these reasons and letting aside further considerations on the theoretical suitability of the distinction between therapy and enhancement for the purposes of identifying permissible uses of HHGE, I believe that it is worth trying to define the concept of therapy, and those strictly related of disease and health.
3.1 The Definitions of Therapy, Health, and Disease
Definitions of “enhancement” may be sorted into 4 broad categories: (a) enhancement defined as the use of a technique originally developed for therapeutic purposes, but that goes beyond it (“beyond therapy views”); (b) quantitative approach, when the technique is used to increase or add certain capabilities; (c) qualitative approach, i.e., making human traits somehow better; and (d) enhancement defined as an “umbrella term” for a number of particular potential changes.59 Indeed, enhancement has been defined as “interventions different from treating human disease,”60 “interventions that extend targeted traits or capabilities beyond the normal range,”61 or “intervention with the primary aim of overcoming those biological limitations that afflict the average person,”62 and as an intervention used for gaining an “increase of overall well-being rather than an augmentation of single capacities or functions.”63 Finally, Parens defines enhancement as “interventions that improve bodily condition or function beyond what is needed to restore or sustain health,”64 thus focusing on both the technique itself and the aim of its use.65
Similarly, even though definitions of “therapy” vary greatly, they somehow always pivot around the definition of the related concepts of “disease,” “normality/normal functioning” and “health.”66 Indeed, examples of such definitions are the following: “the use of medicine to restore the normal functions of our organism”67 or, specifically for genetic therapy, “manipulation of the genome to treat individuals or their progeny with known diseases, disabilities or impairments to restore them to a normal state of health.”68
Consequently, to properly assess the contours of therapy, it appears that those of “health” and “disease” shall be defined.
3.1.1 Normativist and Naturalist Approach to the Definitions of Health and Disease
In general terms, three approaches might be adopted when it comes to defining what health and disease mean.69 At the two ends of the spectrum, (1) the “naturalist” approach aims at identifying a purely descriptive and value-free definition of health and disease, based exclusively on scientific theories, while (2) the “normativist” approach starts from the assumption that health and disease are concepts inherently value-laden.70 Somehow in between, (3) the hybrid approach tries to reach definitions of these concepts that contain both normativist and naturalist elements.71
Indeed, on the one hand, normativists believe that health and disease are concepts inherently value-laden, because based on the notion of adaptation and environment, and thus an attempt to objectively define them will be vain.72 Indeed, for them the “disease” concept is based on social, moral, and cultural norms,73 and thus absence of diseases is the condition of whoever falls within the boundaries set by such norms.74 By way of example, Downie states that health always requires reference to a certain concept of good life,75 and as for Nordenfelt, “health” is “the ability, given standard circumstances, to reach all his or her vital goals,”76 with “vital goals” being defined as “the set of goals which are necessary and jointly sufficient for a person’s minimal happiness.”77 Along a similar line, the World Health Organisation defines “health” as “a state of complete physical, mental and social wellbeing and not merely the absence of disease or infirmity.”
On the other hand, ‘naturalist’ approaches aim at defining concepts in a purely descriptive manner, thus trying to avoid any kind of evaluative judgements.78 The most prominent influential version of a naturalistic conception of health is Boorse’s biostatistical theory of health (BST),79 with which he aims at defining “health” and “disease” as value-free concepts with an empirical, factual basis in human biology.80 In doing so, he rests on an account of normal physiology, which he considers the basic medical science.
BST defines “disease” as the departure from “species-typical normal functioning,” i.e., the statistically typical contribution of some parts or processes in individuals of a given reference class to survival and reproduction.81 Therefore, the definition of “normality” depends on the statistical distribution of a given characteristics in human beings. Boorse presents his BST according to the following definition schema:82
(a) The reference class is a natural class of organisms of uniform functional design, specifically, an age group of a sex of a species.
(b) A normal function of a part or process within members of the reference class is a statistically typical contribution by it to their individual survival and reproduction.
(c) A disease is a type of internal state which is either an impairment of normal functional ability, i.e., a reduction of one or more functional abilities below typical efficiency, or a limitation on functional ability caused by environmental agents.
(d) Health is the absence of disease.
Therefore, in simplified terms, an individual is
diseased when one of the relevant functions is performed below the statistical norm of the same species reference class on species-typical occasions;83
healthy in the absence of diseases as above defined and thus if “all the functions that contribute to the species member’s survival and reproduction today are capable of performing in a way that is species-typical (i.e., the statistical norm of the relevant functions of the same species, sex and age at time t) on species typical occasions.”84
Consequently, “therapeutic” is any intervention whose aim is to restore an individual’s function capability to the species-typical normal range, defined in statistical, naturalistic,85 and objective terms.86
Therefore, it seems that in his BST Boorse resorts to physiology and statistics (and statistical normalcy) to avoid value-laden judgements on the concept of “health” and “disease.”
However, through time, this approach has been the target of many criticisms.
First of all, it has been asserted that, because of the reliance of Boorse’s BST on statistical normalcy, changes in the status of an individual as healthy or diseased depend not only on physiological changes in the individuals themselves, i.e., on the fact that now a relevant function fails to perform in a way that is species-typical differently from before, but also on mere “Cambridge changes.”87 Changes of this kind occur in the absence of “real” physiological changes in the individual, but whenever there is a statistical change in the norm of a relevant function for a reference class.88 This tendency to be prone to Cambridge changes undermines the objectivity of Boorse’s approach.
Secondly, scholars highlighted the difficulties in defining which human traits shall be deemed to be “normal.” Indeed, human traits and their development are the result of interactions between genotypes and various complex non-genetic environmental factors.89 Even though we can identify different statistical patterns of traits development, we cannot objectively define which of these is normal for a given species.90 Therefore, it has been argued that Boorse’s theory rests on some idealized standard which has been developed recurring to moral values and against which dysfunctions are measured. Indeed, also the choice of the appropriate degree of departure from normal functionality (if ever defined) may, in fact, be normatively determined.91 For this reason too, Boorse’s naturalistic approach has been criticized as being in fact value-laden and thus failing to achieve a properly objective notion of disease.92
Finally, with the intention of building a middle ground approach for defining “disease,” which includes both bio-functional and value elements of the disease concept, Wakefield proposed the category of “harmful dysfunction.” In this proposal, harmfulness shall be interpreted according to social values, while the existence of disfunctions shall be evaluated in biological terms as the failure to perform one’s evolutionary function.93
3.2 On the Definitory Approach to be Adopted for Assessing the Permissibility of HHGE
When it comes to define health and disease for the purpose of assessing the lawfulness of HHGE, naturalism seems to be the preferable option, at least theoretically. Indeed, “there seems good reason, (…) to seek an objective framework, so that judgments of health and disease are removed from the subjective domain where contentious disputes leading to personal or social abuses are more likely.”94 However, as extensively discussed above, only value-laden approaches for defining concepts such as therapy, health, and disease appears to be possible. Indeed, any attempt to reach naturalistic definitions of such concepts seems to fail its original purpose of being entirely value-free.
Therefore, a normative approach seems to be the only feasible option, which however might be problematic for at least two different reasons.
First of all, as we have seen normativism prioritizes an approach which takes into account also the person’s perception of his/her health condition. However, in the context of HHGE “disease” and “health” are concepts referred to a future person, and therefore it is impossible to include such parameter in the decision of whether to permit specific interventions. Thus, such evaluation would be performed by third parties on behalf of the person to be born. It would then become possible for prospective parents to choose to alter some traits for no scientific medical reason, if driven by the belief that this genetic modification would enable their child to live an appropriate life. Decisions of this kind may be in contrast with the right to an open future of the future person,95 and his/her human dignity.96
Moreover, in the context of HHGE normativism might lead to discriminatory decisions by public authorities and be considered as a step towards state-driven eugenics. Indeed, “if definitions of health and disease are based on judgments of what is desirable and undesirable, on approval or disapproval, without reference to objective standards, there is considerable potential for mistreatment of individuals or groups.”97 The lack of clear, predetermined criteria based on empirical evidence might lead to a discretionary sorting between desirable and undesirable traits by public authorities, as well as arbitrary decision on the social, moral, and cultural norms to be taken as parameters to evaluate whether to correct a specific genetic alteration might be said to prevent the occurrence of a disease, thus being therapeutic.
However, it might be said that the impact of the issues arising from the adoption of a value-laden definition of health and disease might be mitigated by the introduction of the threshold of the seriousness of the disease when assessing the legitimacy of HHGE interventions. By doing so, HHGE would be lawfully used to correct not any genetic alteration responsible for the outbreak of a disease (value-laden defined), but only those that would cause a serious disease. However, even though the seriousness of the disease is often cited by scholars or institutions in international documents or statements as a threshold for assessing the permissibility of HHGE, and sometimes included in regulations on other IVF technologies, I will now argue that it could not serve the goal of limiting the discretion embedded in a value-laden definition of the concepts of health and disease.
3.3 The Threshold of the Seriousness of the Disease
The seriousness of the disease is a cornerstone notion in many public policies.98 As outlined above, it has been used on different occasions also in the debate on the permissibility of HHGE in the NASEM99 Report and by the German Ethics Councils,100 to cite a few, and it is often referred to as a criterion to sort between legitimate and unlawful uses of many biomedical interventions, in the sense that permissible uses of a given technology are only those aiming at treating (genetic) diseases that meet a certain level of seriousness. Indeed, as a matter of example, this “serious factor” is embedded in regulations on PGD and therapeutic abortion, biomedical interventions which raise moral and legal concerns like those surrounding HHGE.
The reason for its introduction may be linked to the need of somehow protecting the in-vitro embryos. Indeed, in this regard, while not answering the question of whether an embryo may be qualified as “person” for the meaning of Article 2 of the ECHR,101 the European Court of Human Rights stated in the case Vo. v. France that embryos “are beginning to receive some protection in the light of scientific progress and the potential consequences of research into genetic engineering, medically assisted procreation or embryo experimentation.”102 Being worth of protection, some regulations allow the use of certain IVF techniques that directly affect the embryo only in relation to diseases that meet a certain level of seriousness.
However, I believe that the “serious factor” should not be used in the context of HHGE as a mean for limiting the level of discretion included in a value-laden definition of health and disease, because of two reasons: (1) a value-free and empirical definition of this concept cannot be reached, and (2) the creation of a list of diseases that meet such threshold may in itself lead to further discrimination and stigmatization.
Indeed, on the one hand regulations and public opinions never attempt to properly define what seriousness means.103 It has been thus suggested that lawmakers might have referred to a hypothetical “common public understanding of what constitutes a serious disorder,” which has been proved to be absent.104 Scholars on the matter are almost unanimous in asserting that a value-free or empirical definition of seriousness is impossible to be reached. Indeed, the threshold of seriousness of the disease is often criticised for being an ontologically vague, subjective, and arbitrary concept,105 because of the lack of consensus on its core elements, the heterogenous perception of diseases,106 and its reliance on socio-economic factors.107 Moreover, from a critical disability rights perspective, Asch, Parens, and Saxton claimed that such concept is socially construed and reflects existing biases and misconceptions in society.108
On the other hand, a list of diseases that meet the threshold of the seriousness of the disease may be drawn up to avoid the need to provide for an abstract definition of the concept, as for example suggested by Recommendation 934 of the Council of Europe.109 A similar approach has been adopted by UK, where the HFE Authority is responsible for drawing up and updating a list of serious genetic diseases for which undergoing PGD is considered lawful.110 The decision on the granting of the licenses to conduct PGD were originally taken on a case-by-case basis, while nowadays this assessment is being conducted on a condition-by-condition basis: Once a condition has been included in the list of those for the detection of which PGD may be performed, subsequent requests for undergoing PGD for the same disease may rely on this first assessment.111
However, in general, Member States that allow PGD usually refuse to draw up a list of this kind because of the fear of possible stigmatization and discrimination.112 Letting aside questions on the criteria to be defined to assess whether a specific disease qualifies as “serious,” the very idea of creating a list of diseases that meet the “serious” threshold is problematic.113 Indeed, the disability community raised concerns on the possible discriminatory effects that a list of this kind may generate.114 As Parens and Asch stated “it increases the likelihood that an explicitly devaluing message will be sent about people whose conditions are listed as ‘serious enough to avoid’.”115
4 Alternative Methods to Assess the Permissibility of HHGE — The PGD Model
As extensively discussed above, adopting a value-laden definition of the concepts of therapy, health, and disease may raise issues mainly related to (1) the lack of legal certainty on the criteria used to assess the permissibility of HHGE, (2) possible arbitrary decisions and discriminatory effects. Moreover, these issues cannot be mitigated or solved through the use of the “serious factor.”
The aim of this Section is thus to evaluate a different method for assessing when HHGE might be permissible, namely, to adopt the same legal boundaries and thresholds delineated by the regulation on PGD (the so-called “PGD model”).116
Regulations on PGD among national legislations vary greatly, and even among EU Member States.117 However, in those countries where it is a lawful procedure, its use is mainly restricted to the detection (and thus avoidance) of serious genetic diseases.118 By way of example, in France an authorization to undergo PGD may be granted only if the couple has a high probability of giving birth to a child affected by a particularly serious genetic disease recognized as incurable at the moment of the diagnosis.119 Moreover, in Germany PGD is allowed only in case of high risk of a serious hereditary genetic disease.120
Therefore, applying the PGD model would mean to decide whether to allow HHGE by using exactly and only the same line of reasoning adopted to determine whether a certain genetic condition is serious enough to permit the screening, and subsequent discard, of an in-vitro embryo. No other elements would be considered in the evaluation. However, this approach might be subject to the following criticisms.
Firstly, PGD is an invasive procedure for the embryo tested, and it is undergone with the only purpose of operating a negative selection, namely to discard those embryos that are affected by the unwanted genetic alteration.121 On the contrary, the purpose of HHGE “is clearly therapeutic,”122 in the sense that it may be used to prevent the birth of a child with a genetic disease of which he/she was a carrier. While it is true that both PGD and HHGE permit to avoid the birth of an unhealthy person, only HHGE may be used to allow the birth of a healthy child.123 Consequently, on the one hand it seems reasonable to restrict the permissible use of PGD to the avoidance of only serious genetic diseases. In this way, the range of possible defects that permits the use PGD are limited to those cases where the seriousness of the condition justifies the decision not to implant an (unhealthy) embryo with the aim of safeguarding parental rights and interests. Among the latter, it is worth mentioning the right to conceive a child unaffected by a specific genetic disease, which is worth of protection under Article 8 of the ECHR, even though not directly enshrined in the Convention.124 On the other, the same cannot be said for HHGE, which may be used to promote the life and health of a future person by allowing her birth.
Therefore, considering that “the value of HHGE comes mainly from its ability to go much further than what PGD is and will be able to accomplish,” “limiting its applicability to serious diseases is depriving the technique of its raison d’être.”125
However, I believe that a possible solution might be to adopt the PGD model not as the only method to assess the permissibility of HHGE, but as a complementary one. Indeed, I propose to use the PGD model as a “minimum threshold,” namely, to allow HHGE at least whenever used to correct a genetic defect for which PGD is possible.
This approach derives from the idea that, as explained above, unlike PGD HHGE may be used to correct a genetic defect responsible for a specific genetic disease and thus to enable the birth of a healthy child who otherwise would never have come into existence. Indeed, if PGD detects a genetic defect, the “unhealthy” embryos are usually discarded and not chosen for implantation. In this regard, some national regulations even explicitly prohibit to choose to implant “unhealthy” embryos over healthy ones if the latter are available after an IVF cycle.126 Even if it is true that this is not the case for every regulatory framework on PGD, and thus that some countries may permit to implant an “unhealthy” embryo, it seems unreasonable to establish that for certain genetic diseases PGD and the subsequent decision not to implant affected embryos are permissible, while eliminating such genetic defect and consequently implant the modified embryo afterwards are not.127
Indeed, it seems reasonable to allow HHGE whenever used for correcting genetic diseases for which it is permissible to undergo PGD and discard the “unhealthy” embryos in case of positive result. In these eventualities, HHGE would not only be a form of prevention of diseases and promotion of health of the person-to-be, but also a mean to the end of giving birth to a healthy child.
5 Conclusion
In this paper, I have advocated that the distinction between therapeutic purpose and enhancement is still worth studying for the purposes of assessing permissible uses of HHGE. However, there is still no agreement on the definition of such concepts.
In particular, the notion of therapy rests on two further concepts, those of health and disease, which shall firstly be defined to determine the contours of the notion of therapeutic purpose. Two main approaches might be identified to this end, the value-free/naturalistic and the value-laden ones. While in theory the first is preferrable for the purpose of identifying permissible uses of HHGE, value-free approaches fail in principle to completely avoid the use of value-laden concepts. However, adopting a “normativist” approach may raise concerns related to the lack of legal certainty on the elements to be considered when conducting such assessment and may possibly result in arbitrary decisions with discriminatory effects. Neither the adoption of the threshold of the seriousness of the disease may serve the goal of reducing such discretion and eliminating the problems raised by a value-laden approach, given the impossibility to define such concept in value-free terms and the fact that drawing up a list of possible diseases for which HHGE is in principle admissible may contribute to further stigmatization and increase in itself possible discriminatory effects.
Indeed, a different method might be proposed, that of the so called PGD model, i.e., to apply the regulation on PGD to assess the permissibility also of HHGE. However, existing differences between the two techniques may jeopardize this approach, if the PGD model is used as the only criterion for assessing the permissibility of HHGE. Indeed, only HHGE may be used to allow the birth of a healthy child, while PGD may exclusively serve the goal of avoiding the birth of a (possibly) unhealthy one. However, finally, I suggest that this model should not be abandoned altogether. In fact, if the technique is found safe and effective for clinical application, HHGE should be permitted at least for correcting those genetic diseases for which PGD is legitimate, thus implementing the PGD model as a minimum threshold for HHGE.
B. Fantini, ‘Il fantasma dell’eugenetica’, in S. Rodotà (ed.) Questioni di bioetica (Bari: Laterza, 1993).
M. Mcnutt, ‘Breakthrough to Gernome Editing’, Science 350 (6267) (2015) 1445, doi: 10.1126/science.aae0479.
A. Boggio, ‘Introduction’, in A. Boggio, C. Romano and J. Almqvist (eds.), Human Germline Genome Modification and the Right to Science: A Comparative Study of National Laws and Policies (Cambridge: Cambridge University Press, 2020), pp. 1–21, doi: 10.1017/9781108759083.002.
National Academy of Sciences, Heritable Human Genome Editing (Washington, DC: The National Academies Press, 2020), https://doi.org/10.17226/25665.
Supra note 3.
For an extensive analysis of the ethical and legal concerns related to the use of HHGE for enhancement see, among others, National Academies of Sciences, Engineering, and Medicine, Human Genome Editing: Science, Ethics, and Governance (Washington, DC: The National Academies Press, 2017), doi: 10.17226/24623; Nuffield Council on Bioethics, Genome Editing and Human Reproduction: social and ethical issues (London: Nuffield Council on Bioethics, 2018); C Gyngell, T. Douglas and J. Savulescu, ‘The ethics of germline gene editing’, Journal of Applied Philosophy, 32 (4) (2017) 498–513, doi: 10.1111/japp.12249.
For a more in-depth analysis, see German Ethics Council, Intervening in the Human Germline. Opinion — Executive Summary & Recommendations (Berlin: German Ethics Council, 2019) and European Group on Ethics in Science and New Technologies, Opinion on Ethics of Genome Editing — Opinion n. 34 (Brussels: European Group on Ethics in Science and New Technologies, 2021).
Supra note 7.
Supra note 6.
Nuffield Council on Bioethics, supra note 6.
R. Andorno and E.A. Yamin, ‘The Right to Design Babies? Human Rights and Bioethics’, OpenGlobalRights (2019), available online at https://www.openglobalrights.org/the-right-to-design-babies-human-rights-and-bioethics/. In this regard, see also in particular Parliamentary Assembly of the Council of Europe, ‘The Use of New Genetic Technologies in Human Beings’, Recommendation 2115 (2017) where it is stated: “3. Deliberate germ-line editing in human beings would cross a line viewed as ethically inviolable.”
For an extensive analysis of the national regulations on HHGE see F. Baylis, M. Darnovsky, K. Hasson and T.M. Krahn, ‘Human Germline and Heritable Genome Editing: The Global Policy Landscape’, The CRISPR Journal 3(5) (2020) 365–377, doi: 10.1089/crispr.2020.0082.
J.B. Hurlbut, ‘Human Genome Editing: Ask Whether, Not How’, Nature 565 (135) (2019) 135, doi: https://doi.org/10.1038/d41586-018-07881-1; D. Dickenson and M. Darnovsky, ‘Did a Permissive Scientific Culture Encourage the “CRISPR Babies” Experiment?’, Nature Biotechnology 37 (2019) 355–357, doi: 10.1038/s41587-019-0077-3; E.Y. Adashi and I.G. Cohen, ‘Heritable Genome Editing: Is a Moratorium Needed?’, Journal of the American Medical Association 322 (2) (2019) 104–105, doi: 10.1001/jama.2019.8977. Admittedly, Stock and Campbell were already asking the same question back in 2000; G. Stock and J. Campbell, Engineering the Human Germline: An Exploration of the Science and Ethics of Altering the Genes We Pass to Our Children (Oxford: Oxford University Press, 2000), p. 6.
R. Isasi, E. Kleiderman and B.M. Knoppers, ‘Editing policy to fit the genome’, Science 351 (6271) (2016) 337–339, doi: 10.1126/science.aad6778.
L. Lu, ‘Recent advances in preimplantation genetic diagnosis and screening’, Journal of Assisted Reproduction and Genetics 33 (2016) 1129–1134, doi: 10.1007/s10815-016-0750-0.
E. Kleiderman, V. Ravitsky and B.M. Knoppers, ‘The “serious” factor in germline modification’, Journal of Medical Ethics 45 (2019) 508–513.
C Kuppuswamy, The International Legal Governance of the Human Genome (Abingdon: Routledge, 2009).
R. Andorno, Principles of International Biolaw: Seeking Common Ground at the Intersection of Bioethics and Human Rights (Brussels: Bruylant, 2013).
This position was then reaffirmed in 2003 by the Report of the IBC on pre-implantation genetic diagnosis and germ-line intervention.
J. Almqvist, ‘The Regulation of Human Germline Genome Modification in Europe’, in A. Boggio, C. Romano and J. Almqvist (eds.), Human Germline Genome Modification and the Right to Science: A Comparative Study of National Laws and Policies (Cambridge: Cambridge University Press, 2020), pp. 155–216, doi: 10.1017/9781108759083.007. However, it is worth noticing that the Convention is binding exclusively upon the States that fully ratify it. Nowadays, the Convention has been ratified by 29 countries and signed, but not yet fully ratified, by a further 7.
Article 13: “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.” On the interpretation of this Article as a categorical ban on HHGE see Oviedo Convention, Explanatory Report (no. 20), para. 90. On a more in-depth analysis of Article 13 and different interpretations of its meaning, see supra note 20.
Explanatory Report to the Convention on Human Rights and Biomedicine, European Treaty Series, no. 164, sub 89.
Parliamentary Assembly of the Council of Europe, ‘Recommendation on Genetic Engineering’, Recommendation 934 (1982), sub 4a.
Ibid., sub 4.
Ibid., sub 4e and 4f.
Parliamentary Assembly of the Council of Europe, supra note 11.
For a more comprehensive analysis of the different national regulations on HHGE, A. Boggio, C. Romano and J. Almqvist (eds.), Human Germline Genome Modification and the Right to Science: A Comparative Study of National Laws and Policies (Cambridge: Cambridge University Press, 2020); and Baylis et al., supra note 12.
ESchG para. 5(1) and (2).
Law 40/2004 Article 14.
Law 40/2004 Article 13 para. 3 lett. b.
Code Civile Article 16–4.
Act 3148/2005 Article 34.
X. Kang, W. He, Y. Huang, Q. Yu, Y. Chen, X. Gao, X. Sun and Y. Fan, ‘Introducing precise genetic modifications into human 3PN embryos by CRISPR/Cas-mediated genome editing.’ Journal of Assisted Reproduction and Genetics 33 (5) (2016) 581–588, doi: 10.1007/s10815-016-0710-8; P. Liang, Y. Xu, X. Zhang, C. Ding, R. Huang, Z. Zhang, J. Lv, X. Xie, Y. Chen, Y. Li, Y. Sun, Y. Bai, S. Zhou, W. Ma, C. Zhou and J. Huang, ‘CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes.’ Protein & Cell 6 (5) (2015) 363–372, doi: 10.1007/s13238-015-0153-5.
By way of example, S. Chan, P.J. Donovan, T. Douglas, C. Gyngell, J. Harris, R. Lovell-Badge, D.J.H. Mathews, A. Regenberg and On Behalf of the Hinxton Group, ‘Genome Editing Technologies and Human Germline Genetic Modification: The Hinxton Group Consensus Statement’, The American Journal of Bioethics 15(12) (2015) 42–47, doi: 10.1080/15265161.2015.1103814; D. Baltimore, P. Berg, M. Botchan, D. Carroll, R.A. Charo, G. Church, J.E. Corngeorge Q. Daleyjennifer A. Doudna Marsha Fennerhenry T. Greelymartin Jinekg. Steven Martinedward Penhoet, J. Puck, S.H. Sternberg, J.S. Weissman and K.R. Yamamoto, ‘Biotechnology. A prudent path forward for genomic engineering and germline gene modification’, Science 348 (6230) (2015) 36–38, doi: 10.1126/science.aab1028; Lanphier, F. Urnov, S. Ehlen Haecker, M. Werner and J. Smolenski, ‘Don’t edit the human germ line’, Nature 519 (2015) 410–411, doi: 10.1038/519410a; Berlin-Brandenburg Academy of Sciences and Humanities (BBAW), Human Genome Surgery — Towards a Responsible Evaluation of a New Technology (Berlin: BBAW, 2015); Leopoldina, Acatech and Union, The opportunities and limits of genome editing (Halle/Saale: Leopoldina, 2015).
Chan et al., supra note 34.
Ibid.
E. Callaway, ‘UK scientists gain licence to edit genes in human embryos’, Nature 530 (2016) 18, doi: 10.1038/nature.2016.19270.
‘Human Germline Genome Editing’, UK Parliament Post 611 (January 2020).
H. Devlin, ‘Baby with DNA from three people born in Greece’, The Guardian (2019).
Supra note 4.
Extensively on this topic, Committee on the Ethical and Social Policy Considerations of Novel Techniques for Prevention of Maternal Transmission of Mitochondrial DNA Diseases, Mitochondrial Replacement Techniques: Ethical, Social, and Policy Considerations (Washington, DC: National Academies Press, 2016), doi: 10.17226/21871; H. Sharma, D. Singh, A. Mahant, S.K. Sohal, A.K. Kesavan and Samiksha, ‘Development of mitochondrial replacement therapy. A review’, Heliyon 6 (9) (2020) e046043, doi: 10.1016/j .heliyon.2020.e04643; supra note 4.
B.C. van Beers, ‘Rewriting the human genome, rewriting human rights law? Human rights, human dignity, and human germline modification in the CRISPR era’, Journal of Law and the Biosciences 7 (1) (2020) lsaa006, doi: 10.1093/jlb/lsaa006.
J. He, About Lulu and Nana: Twin girls born healthy after gene surgery as single-cell embryos (2018), available online at https://www.youtube.com/watch?v=th0vnOmFltc&t=18s (accessed 28 December 2020).
E.S. Lander, ‘Brand new genome’, The New England Journal of Medicine 373 (1) (2015) 5–8, doi: 10.1056/NEJMp1506446.
R. Alta Charo, ‘Rogues and regulation of germline editing’, The New England Journal of Medicine 380 (2019) 976–980, doi: 10.1056/NEJMms1817528. Along the same line of reasoning, P. Sykora and A. Caplan, ‘The Council of Europe should not reaffirm the ban on germline genome editing in human’, EMBO Reports 18 (2017) 1871–1872, doi: 10.15252/embr.201745246; G. De Wert, B. Heindryckx, G. Pennings, A. Clarke, U. Eichenlaub-Ritter, C.G. van El, F. Forzano, M. Goddijn, H.C. Howard, D. Radojkovic, E. Rial-Sebbag, W. Dondorp, B.C. Tarlatzis and M.C. Cornel, ‘Responsible innovation in human germline gene editing: background document to the recommendations of ESHG and ESHRE’, European Journal of Human Genetics 26 (2018) 450–470; supra note 10.
P. Dabrock, ‘Who? What? How? Why? If You Don’t Ask, You’ll Never Know … On Criticism of the New Uproar about Germline Editing — Discourse Analytical and Socioethical Metaperspectives’, in: M. Braun, H. Schickl, P. Dabrock (eds.), Between Moral Hazard and Legal Uncertainty — Ethical, Legal and Societal Challenges of Human Genome Editing (Wiesbaden: Springer Nature, 2018), pp. 163–186.
National Academies of Sciences, Engineering, and Medicine, supra note 6.
National Academies of Sciences, Engineering, and Medicine, ‘Second International Summit on Human Genome Editing: Continuing the Global Discussion: Proceedings of a Workshop — in Brief ’ (Washington, DC: The National Academies Press, 2019), doi: 10.17226/25343.
Ibid.
Berlin-Brandenburg Academy of Sciences and Humanities (BBAW), Fourth Gene Technology Report — Review of a High-Tech Sector (Berlin: BBAW, 2019); E. Lander, F. Baylis, F. Zhang, E. Charpentier, P. Berg, C. Bourgain, B. Friedrich, J.K. Joung, J. Li, D. Liu, L. Naldini, J.-B. Nie, R. Qiu, B. Schoene-Seifert, F. Shao, S. Terry, W. Wei and E.-L. Winnacker, ‘Adopt a moratorium on heritable genome editing’ Nature 567 (2019) 165–168, doi: 10.1038/d41586-019-00726-5.
Among many others, E. Juengst, ‘Can enhancement be distinguished from prevention in genetic medicine?’ Journal of Medicine and Philosophy 22 (1997) 125–142, doi: 10.1093/jmp/22.2.125; W. Anderson, ‘Human gene therapy: scientific and ethical considerations’, Journal of Medicine and Philosophy, 10 (1985) doi: 10.1093/jmp/10.3.275.
A.M. Gouw, ‘Challenging the Therapy/Enhancement Distinction in CRISPR Gene Editing’, in: The Palgrave Handbook of Philosophy and Public Policy (Basinstoke: Palgrave, 2018), pp. 493–508, doi.org/10.1007/978-3-319-93907-0_38; B. Cwik, ‘Moving Beyond “Therapy” and “Enhancement” in the Ethics of Gene Editing’, Cambridge Quarterly of Healthcare Ethics 28 (4) (2019) 695–707, doi: 10.1017/S0963180119000641.
Nuffield Council on Bioethics, supra note 6.
Of a different opinion, see, among others, Cwik, supra note 52; R. Bjerregaard Mikkelsen, H. Reventlow S Frederiksen, M. Gjerris, B. Holst, P. Hyttel, Y. Luo, K. Freude and P. Sandøe, ‘Genetic Protection Modifications: Moving Beyond the Binary Distinction Between Therapy and Enhancement for Human Genome Editing’, CRISPR Journal 2 (6) (2019) 362–369, doi: 10.1089/crispr.2019.0024.
Along the same line, but in general for biomedical interventions, A. Giubilini, ‘Normality, Therapy, and Enhancement: What Should Bioconservatives Say about the Medicalization of Love?’, Cambridge Quarterly of Healthcare Ethics 24(3) (2015) 347–354. doi: 10.1017/S0963180114000656. However, it is worth mentioning that the Nuffield Council of Bioethics rejected the therapy/enhancement distinction and stated that the guiding principle in deciding on the permissibility of HHGE should be the best interest of the (future) child. It goes without saying that this line of reasoning led the Council to declare that at least in principle HHGE may also be used for enhancement. See supra note 6.
National Academy of Sciences supra note 4. The purpose of the Report was to determine criteria for developing sufficient safety and efficacy of genome editing methodology for responsible clinical use, and not to establish whether HHGE techniques should in principle be permitted.
BBAW, Leopoldina, Acatech and Union supra note 34. For some scholars, we have a moral obligation to use HGGE for disease prevention. On this further topic, Gyngell et al., supra note 6.
T. Ishii, ‘Germ Line Genome Editing in Clinics: The Approaches, Objectives and Global Society’, Briefings in Functional Genomics 16 (2017) 46–56; C. Long, J.R. McAnally, J.M. Shelton, A.A. Mireault, R. Bassel-Duby and E.N. Olson, ‘Prevention of Muscular Dystrophy in Mice by CRISPR/Cas9-Mediated Editing of Germline DNA’, Science 345 (2014) 1184–1188; National Academies of Sciences, Engineering, and Medicine supra note 6, p. 159.
R. Chadwick, ‘Therapy, Enhancement and Improvement’, in: B. Gordijn, R. Chadwick (eds.) Medical Enhancement and Posthumanity (Berlin: Springer, 2009), pp. 25–37.
Ibid.
Bjerregaard Mikkelsen et al., supra note 54.
D. Greenbaum and L.Y. Cabrera (eds.), ELSI in Human Enhancement: What Distinguishes it from Therapy? (Lausanne: Frontiers Media, 2020), p. 1, doi: 10.3389/978-2-88966-221-0.
J. Savulescu, ‘Justice, fairness, and enhancement’, Annals of the New York Academy of Sciences 1093 (2006) 321–338, doi: 10.1196/annals.1382.021; B.D. Earp, A. Sandberg, G. Kahane and J. Savulescu, ‘When is diminishment a form of enhancement? Rethinking the enhancement debate in biomedical ethics’, Frontiers in Systems Neuroscience 8 (12) (2014) 1–8, doi: https://doi.org/10.3389/fnsys.2014.00012.
National Academies of Sciences, Engineering, and Medicine supra note 6, p. 145.
Ibid.
Supra note 55.
Ibid.
Gouw, supra note 52.
M. Ereshefsky, ‘Defining “Health” and “Disease”’, Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences 40 (3) (2009) 221–227, doi: 10.1016/j.shpsc.2009.06.005.
R.P. Hamilton, ‘The concept of health: beyond normativism and naturalism’, Journal of Evaluation in Clinical Practice 16 (2) (2010) 323–329, doi: 10.1111/j.1365-2753.2010.01393.x.
Ibid.
J. Kovács, ‘The concept of health and disease’, Medical Health Care Philosophy 1 (1998) 31–39, doi: 10.1023/A:1009981721055.
D.B. Resnik, ‘The moral significance of the therapy-enhancement distinction in human genetics’, Cambridge Quarterly of Health Ethics 9 (3) (2000) 365–377, doi: 10.1017/s0963180100903086.
Ibid.
K.M. Boyd, ‘Disease, illness, sickness, health, healing, and wholeness: exploring some elusive concepts’, Medical Humanities 26 (1) (2000) 9–17, doi: 10.1136/mh.26.1.9.
L. Nordenfelt, ‘The Concepts of Health and Illness Revisited’, Medicine, Healthcare and Philosophy 10 (2007) 5–10.
L. Nordenfelt, On the Nature of Health. An Action Theoretic Approach (Dordrecht: Kluwer Academic Publishing, 1995). Various critiques were made through time by scholars. Indeed, it has been pointed out that a broad definition of this kind ‘leaves most of us unhealthy most of the time’, as pointed out by R. Smith, ‘The end of disease and the beginning of health’, The BMJ Opinion (8 July 2008), available online at https://blogs.bmj.com/bmj/2008/07/08/richard-smith-the-end-of-disease-and-the-beginning-of-health/.
R. Powell and E. Scarffe, ‘Rethinking “Disease”: a fresh diagnosis and a new philosophical treatment’, Journal of Medical Ethics 45 (2019) 579–588.
J.D. Guerrero, ‘On a naturalist theory of health: a critique’, Studies in History and Philosophy of Science Part C41 (3) (2010) 272–278, doi: 10.1016/j.shpsc.2009.12.008; T. Schramme, ‘What a Naturalist Theory of Illness Should Be’, in: E. Giroux (ed.), Naturalism in the Philosophy of Health (Berlin: Springer, 2016), pp. 63–77, doi: 10.1007/978-3-319-29091-1; Powell and Scarffe, supra note 78.
R.M. Sade, ‘A Theory of Health and Disease: The Objectivist-Subjectivist Dichotomy’, The Journal of Medicine and Philosophy 20 (1995) 513–525.
Powell and Scarffe, supra note 78. Indeed, they firmly state that the only biological mechanisms relevant to properly defined health and disease are those that contribute to individual survival and reproduction. Such assumption, far from being normative or value-laden, derives from the evidence that ‘human physiologists have as yet found no functions clearly serving species survival rather than individual survival and reproduction’. C. Boorse, ‘A rebuttal on health’, in: J.M. Humber and R.F. Almeder (eds.), What is disease? (Totowa, NJ: Humana Press, 1997), pp. 3–134. Of a different opinion, Ereshefsky, supra note 69.
Boorse, supra note 81.
Guerrero, supra note 79.
Ibid.
M. Lemoine and É. Giroux, ‘Is Boorse’s Biostatistical Theory of Health Naturalistic?’, in: E. Giroux (ed.), Naturalism in the Philosophy of Health (Berlin: Springer, 2016), pp. 19–38.
For a more in-depth analysis of his theory, see supra notes 72, 74 and 80.
Guerrero, supra note 79.
Ibid.
R. Amundson, ‘Against normal function’, Studies in History and Philosophy of Science Part C 31 (2000) 33–53.
Supra note 74.
Powell, supra note 78.
Ibid.
Supra note 78; J.C. Wakefield, ‘Disorder as harmful dysfunction: a conceptual critique of DSM-III-R’s definition of mental disorder’, Psychology Reviews 99 (1992) 232–247.
Supra note 80.
J. Feinberg, ‘The child’s right to an open future’, in: J. Feinberg (ed.), Freedom and Fulfilment (Princeton, NJ: Princeton University Press, 1992), pp. 221n235.
Supra note 73.
Supra note 80.
D.C. Wertz and B.M. Knoppers, ‘Serious genetic disorders: can or should they be defined?’ American Journal of Medical Genetics 108(1) (2002) 29–35, doi: 10.1002/ajmg.10212.
National Academies of Sciences, Engineering, and Medicine, supra note 6.
German Ethics Council, supra note 7.
Vo. v. France App No 53924/00 8 July 2004, para. 85.
Ibid., para. 82.
However, see Kleiderman, supra note 14, where it is stated that “The U.S. Food and Drug Administration defines ‘serious’ as ‘a disease or condition associated with morbidity that has substantial impact on day-to-day-functioning. Short-lived and self-limiting morbidity will usually not be sufficient, but the morbidity need not be irreversible, provided it is persistent or recurrent. Whether a disease or condition is serious is a matter of clinical judgement, based on its impact on such factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one.’”
Supra note 98.
Ibid. and supra note 103.
F.K. Boardman and C.C. Clark, ‘What is a “serious” genetic condition? The perceptions of people living with genetic conditions’, European Journal of Human Genetics (2021) 160–169, doi: 10.1038/s41431-021-00962-2.
Supra note 98.
M. Saxton, ‘Disability rights and selective abortion’, in: L.J. Davis (ed.), The Disability Studies Reader (Hove: Psychology Press, 2006), pp. 105–116; E. Parens and A. Asch, ‘The Disability Rights Critique of Prenatal Genetic Testing Reflections and Recommendations’, The Hastings Center Report 29 (5) (1999) S21–S22, doi: 10.2307/3527746.
“Provide for the drawing up of a list of serious diseases which may properly (…) be treated by gene therapy,” supra note 23.
V. English and P. Braude, ‘Regulation of PGD in the UK and Worldwide’, in: T. El-Toukhy and P. Braude (eds.), Preimplantation Genetic Diagnosis in Clinical Practice (Berlin: Springer, 2014); E. Jackson, ‘Statutory Regulation of PGD in the UK: unintended consequences and future challenges’, in: S.A.M. McLean and S. Elliston (eds.), Regulating Pre-implantation Genetic Diagnosis — A Comparative and Theoretical Analysis (Abingdon: Routledge, 2013), pp. 71–88.
Ibid.
W. Manon, Le diagnostic Préimplantatoire et le diagnostic prénatal en Belgique et en France: droit comparé et confrontation aux droits fondamentaux (Louvain: Université Catholique de Louvain, 2019).
In this regard, the International Bioethics Committee asserted that professional organisations of genetics and reproductive technologies, as well as advisory groups on bioethics, opposed to the idea of establishing a list of diseases considered serious enough to justify the use of PGD. See, Comité international de bioéthique, Rapport du CIB sur la mise à jour de sa réflexion sur le génome humain et les droits de l’homme (Paris: CIB, 2015).
J.R. Botkin, ‘Fetal Privacy and Confidentiality’, Hastings Centre Report 25 (5) (1995) 32–39.
Parens, supra note 108.
Kleiderman, supra note 14.
Supra note 14.
Ibid.
Article L2131–4 Code de la Santé Publique.
Section 3a (2) Embryonenschutzgesetz.
R. Ranisch, ‘Germline genome editing versus preimplantation genetic diagnosis: Is there a case in favour of germline interventions?’, Bioethics 34 (1) (2020) 60–69, doi: 10.1111/bioe.12635.
Ibid. Holding the opposite view, T. Rulli, ‘Reproductive CRISPR does not cure disease’, Bioethics 33 (2019) 1072–1082, doi: 10.1111/bioe.12663.
This assumption is based on the subjective evaluation of the effects of PGD and HHGE. Indeed, it is true that also PGD may be used to select healthy embryos to be implanted in a woman, and thus that also such technology may serve the objective purpose of giving birth to a healthy individual. However, the born child (A) is different from the embryo (B) discarded after the diagnosis. On the other hand, HHGE intervenes on the embryo (A) and by correcting its genetic defect enables its birth as a healthy child (A).
Costa and Pavan v. Italy, No. 54270/10, 28 August 2012.
I. De Miguel Beriain, ‘Is the “serious” factor in germline modification really relevant? A response to Kleiderman, Ravitsky and Knoppers’, Journal of Medical Ethics 46 (2019) 151–152, doi: 10.1136/medethics-2019-105744.
HFE Act Section 13 (9).
It is worth reminding that the precondition enshrined in the analysis as a whole is the technique being safe and effective enough for being introduced into clinical practice.