Human dignity and gene editing

Abstract

A common argument against gene editing the human germline is the notion of dignity as linked to the human genome. But this based on a logical fallacy and should rather prompt us to consider gene editing for therapeutic purposes in order to preserve human dignity.

Human germline editing raises a number of essential ethical issues that have spawned intense debate. According to some bioethical arguments and legal documents, germline modification would threaten human dignity, since they consider the human genome as the physical representation [of human dignity]. This article will highlight the inherent contradictions of these arguments and argue that claims that germline editing would violate human dignity are invalid.

… respect for human dignity should actually support arguments to continue with genetic editing of embryos.

The emergence of gene editing technology—particularly CRISPR‐Cas9—and the first experiments to modify the genome of human embryos have given rise to an intense ethical debate. Such an in‐depth discussion of the potential ethical, societal and medical implications is indeed highly relevant as modifications of the germline would not only affect individual patients or humans but the human species as a whole. In fact, the debate began even before the availability of the CRISPS/Cas system when the first gene therapies were developed to cure a few select pathologies. Time has not brought any general agreement, and a universal consensus on whether or not to allow human germline editing is still remote.

The debate

While some commentators call for a total ban on any form of gene editing that affects the human germline 1, others advocate for a moratorium until the risks have been sufficiently addressed and resolved 2. Other authors even claim that germline editing should be considered a moral imperative to improve the human species 3. Similar disagreements exist about the ends to which these techniques should be applied. Some consider that only therapeutic purposes are acceptable; others support their use for human enhancement, a view that many bioethicists and most international declarations and conventions consider as a form of eugenics.

The aim of this article was not to resolve this debate, but to focus on the idea of human dignity and its role in this discussion. Most authors simply assume that respect for human dignity is a crucial argument for opposing germline editing 4. Moreover, even those who disagree with this view have not questioned whether we should accept this postulate as a general moral rule 5.

This paper attempts to show that, in contrast to what is generally accepted, respect for human dignity should actually support arguments to continue with genetic editing of embryos. This article will justify this statement by demonstrating, first, that the arguments in favour of prohibiting genetic manipulation of the germline on the basis of human dignity are not solid. Second, it will explain how the opposite conclusion seems far more reasonable, whatever interpretation of the idea of human dignity we adopt.

Establishing the terms of the debate

A clear definition of human dignity remains elusive, because the concept of dignity is, in itself, extremely problematic to the extent that some people consider that it should be completely omitted from bioethics 6. For the sake of the argument that human dignity should not be an obstacle to genome editing, it is not necessary to delve too deep into this controversy. It is enough to summarize that those who believe in the importance of human dignity and its relation to the human genome generally share three main ideas.

… there is a broad tendency in bioethics to directly link the notion of human dignity to the human genome

The first is that dignity—which is linked to the concept of autonomy—is an intrinsic and non‐negotiable value shared by all human beings, simply by virtue of belonging to the human species. This idea has deep roots in our collective imagination. For instance, it is included in the Universal Declaration of Human Rights of 10 December 1948 whose article 1 states “All human beings are born free and equal in dignity and rights”.

Second, advocates of the idea of human dignity believe that since every human being has the same intrinsic moral value, every person should be treated as though he or she was an end in his or herself and not a mere means. This fundamental idea is based on Kant's moral imperative. Even those who oppose the concept of dignity generally agree—perhaps with the exception of pure utilitarianists—that we cannot instrumentalize human beings. By way of example, the Council of Europe Convention on Action against Trafficking in Human Beings of 16 May 2005 (Warsaw Convention) states in its Preamble “trafficking in human beings constitutes a violation of human rights and an offence to the dignity and the integrity of the human being”.

Third, there is a broad tendency in bioethics to directly link the notion of human dignity to the human genome. Since it is the genome that determines who belongs to the human species and since being part of the human species confers dignity, it seems reasonable to link human dignity to the human genome. For example, the Universal Declaration on the Human Genome and Human Rights adopted by the General Conference of UNESCO on 11 November 1997 states “The human genome underlies the fundamental unity of all members of the human family, as well as the recognition of their inherent dignity and diversity. In a symbolic sense, it is the heritage of humanity” (Article 1).

A major fallacy of arguments based on preserving the human genome is ignoring the fact that the human genome is not a fixed entity…

Having established these fundamental premises, we can now explore the role that the idea of dignity should play with respect to human germline editing. The argument will focus first on one of the main demands by those who wish to ban the application of gene editing in humans: the need to preserve the human genome. The article will then analyse whether a distinction between direct and indirect actions that cause germline changes is reasonable. Finally, it will discuss the implications of banning therapeutic applications in an embryo from the perspective of human dignity.

The need to preserve the human genome

As previously noted, various authors believe that human dignity is intrinsically linked to the human genome. The question then is as follows: What are the normative implications of this belief? The general opinion among opponents of germline editing is that since our dignity is embedded in our genome, we must refrain from altering 7. This idea has received support from the Declaration on the Human Genome and Human Rights (11 November 1997), whose article 24 reads: “The International Bioethics Committee of UNESCO should contribute to the dissemination of the principles set out in this Declaration and to the further examination of issues raised by their applications and by the evolution of the technologies in question. It should organize appropriate consultations with parties concerned, such as vulnerable groups. It should make recommendations, in accordance with UNESCO's statutory procedures, addressed to the General Conference and give advice concerning the follow‐up of this Declaration, in particular regarding the identification of practices that could be contrary to human dignity, such as germ‐line interventions”.

In my opinion, this normative proposal is problematic, because it contradicts the axiom on which it is based: if one believes that our dignity can only remain undiminished if the human genome remains unchanged, we cannot tolerate any new mutation in the human genome—regardless of whether it is produced by human action or naturally. A major fallacy of arguments based on preserving the human genome is ignoring the fact that the human genome is not a fixed entity, an immutable biological substrate, but subject to mutations like any other genome: otherwise, evolution would come to a halt. Even more so, if we claim that respect for human dignity means preserving the human genome in its current state, the logical conclusion would be to not only to renounce sexual reproduction in favour of cloning—as it generates mutations—but even to use gene editing to remove any natural, random mutations because it might violate human dignity and autonomy.

Some would argue that this argument is a sophism: that respect for human dignity does not entail preserving the human genome at all costs; but that humans should not arrogate to themselves the power to alter it 4. But such a rejoinder is at least suspect of a religious or naturalistic component as it implies that only nature or a creator should have dominion over the human genome. The non‐metaphysical alternative in support of this argument is the view that “tried and tested” natural processes are more reliable than “human tinkering” 8. Both assumptions do not hold up to scrutiny.

There is nothing to demonstrate a presumed natural “goodness” or “intelligence”. On the contrary, it seems reasonable to think that editing the human genome to prevent a lethal or devastating disease poses less risk to the future of human beings than changes introduced by the vagaries of random genetic crosses or mutation. Moreover, abstaining from intervention in the human genome when action is possible is already a form of intervention by omission. The emergence of genetic editing means that, whether we like it or not, the human genome will end up being what we decide it to be, by action or by omission. Finally, the idea of dignity is linked to autonomy, that is, the ability to set rules. Trying to renounce this power once it is within our reach is not only almost impossible—knowledge cannot be erased or suppressed—but also implies a refusal to assume the very principle that guarantees human dignity: the ability to impose reasonable human norms on irrational, random nature: a renunciation of autonomy, so to speak.

… even if we were to accept that human dignity and the human genome are linked […] this would not necessarily imply an obligation to preserve the human genome.

In conclusion, even if we were to accept that human dignity and the human genome are linked—which is debatable—this would not necessarily imply an obligation to preserve the human genome. Consequently, there is no reason why we should not proceed to alter the human genome, since it is not a fixed and immutable entity that has to be preserved for the better of humanity. But if we believe the opposite, that we need to conserve the momentary version of the human gene pool, we would have a moral obligation to use genetic editing techniques to reverse the changes brought about by nature. Whatever choice, the belief in a link between the human genome and dignity is not helpful to discuss whether we should allow or ban editing of the human genome.

Changes in the germline

Consider again that we accept the premise that respect for human dignity implies that we must refrain from altering the human genome. If this is the case, should we not then advocate the abolition of any action that would have this effect? Those who argue for the need to preserve the human genome draw a subtle distinction between direct actions that deliberately introduce changes such as gene therapy or therapeutic gene editing and actions that introduce mutations indirectly as a side effect, such as radio‐ or chemotherapy that carry a risk of generating mutations of germline cells.

Indeed, a sizeable number of ethicists and some of our main regulatory instruments argue that direct actions to change the human genome are morally reprehensible and must therefore be illegal. However, interventions that tolerate such changes may be morally acceptable for the sake of defending a greater good. The best example of this principle is the Explanatory Report on the Oviedo Convention, which states: “92. On the other hand the article does not rule out interventions for a somatic purpose, which might have unwanted side‐effects on the germ cell line. Such may be the case, for example, for certain treatments of cancer by radiotherapy or chemotherapy, which may affect the reproductive system of the person undergoing the treatment”.

However, if we accept that our dignity is linked to the human genome and that any change in the latter affects the former, it is not clear why the type of action—direct or indirect—and not its result should be relevant. Is it really pivotal whether the genome has been altered directly or as an inevitable consequence of the action? If human dignity is compromised by the alteration of the human genome, then it clearly does not make a difference. But if so, why should we accept one type of alteration and reject the other?

The fundamental problem is that such conclusions are based on theories of double effect but do not interpret them properly and end up contradicting the importance that human dignity should have. Defenders of involuntary alteration of the human genome argue that if an action is directed at a good end, that is, to save the life of a cancer patient, and that if negative consequence—alteration of the genome or the germline—occurs unintentionally, it is legitimate. However, this notion forgets that the double effect argument includes, as a condition, that the negative consequence must be of minor importance, or at least of proportionally less important than the intended positive effect (literally: “The good effect must be sufficiently desirable to compensate for the allowing of the bad effect” 9). But when the action causes a serious harm to human dignity, it is impossible to apply the principle of double effect, at least if we accept that respect for dignity is an absolute requirement and not a principle that can be waived if circumstances advise so.

Therefore, if we believe that any change in the genome caused by human action is a breach of human dignity, we must refrain from any kind of action that could lead to this consequence whether directly or indirectly—even if this means abolishing radio‐ or chemotherapy. The fact that this appeal does not arise often is a clear inconsistency that can be justified only on pragmatic grounds. But this justification is an unacceptable trick when human dignity is at stake. Last but not least, a consciously caused alteration of the human genome is much closer to the idea of autonomy than is random change brought about by chemotherapy. Again, inconsistencies in the more conservative discourse appear to give a poor answer to this question. Therefore, if we are to accept actions that alter the human genome, even if indirectly, then we have plenty of reasons to consider that those intended to directly produce such a result should also be considered morally acceptable on the basis of human dignity.

Dignity of the embryo

If, in spite of this conclusion, we should persist to veto any alteration of the human genome, it would not necessarily mean refraining from changing the genome of an embryo. This is for one simple reason: there is a big difference between changing the genome of a human being and changing the human genome. This is not dependent on whether it is the genome of one or several human beings, or whether the change occurs in the somatic or germinal line. It depends on the type of alteration. If the final result of the intervention—for instance, replacing a mutated gene to restore its original function—does not introduce any novelty into the human gene pool, then it is inaccurate to speak of an alteration in the human genome.

Imagine, for example, a human embryo with mutations of the Huntington gene that will inevitably lead to Huntington's disease if the embryo grows into a human being. If we edit its germline to replace the gene with a normal variant, we will modify the embryo's genome but not the human genome. The ultimate result of the intervention—a human being with a genome that does not show the specific pathological variant that triggers Huntington's disease—will not introduce any novelty into the human gene pool. Therefore, any appeal not to carry out such intervention on the basis of the defence of the human genome and, hence, human dignity, would be manifestly illogical.

This point could, however, be contested by the argument that although such intervention in itself does not pose a direct threat to human dignity, it could constitute an indirect threat—for example, by enabling other interventions that do alter the human gene pool or even redefine fundamental social relationships (between parents and children, individuals and communities, citizens and states), and associated notions of responsibility and care 10.

… respecting human dignity means putting the individual human and his or her interests before those of his or her possible descendants, social group or the like.

The problem with this kind of argument is that it is disrespectful to what it claims to defend: human dignity. What the argument contends is the following: although we can cure a serious pathology in an embryo or in a human being, we should refrain from doing so in order to preserve higher social values or goods. But is this kind of assertion in line with the fundamental normative principle that follows from the idea of dignity? Is this the proper way to treat an embryo, as an end in itself and not as a mere means to preserve a higher good? Or is this suggestion more like a social eugenics exercise based on the assumption that the interests of the group should prevail over those of the individual? The answer is clear: respecting human dignity means putting the individual human and his or her interests before those of his or her possible descendants, social group or the like. This is laid down in the Universal Declaration on Bioethics and Human Rights of 19 October 2005, whose article 3.2 reads: “The interests and welfare of the individual should have priority over the sole interest of science or society”, which reproduces article 2 of the Oviedo Convention: “The interests and welfare of the human being shall prevail over the sole interest of society or science”. Therefore, respect for human dignity would actually require that we intervene in the human germline in order to preserve the interests of a particular human being, disregarding the collective interest.

Given the logical fallacies, it seems about time to give up on a notion of human dignity and autonomy that is closely linked to the human genome…

The overall conclusion is that there are no good reasons to justify a general ban on genetic editing of the human germline on the basis of human dignity. On the contrary, it is precisely this factor that should prompt us to use genome editing in the interests of the individual human being. Given the logical fallacies, it seems about time to give up on a notion of human dignity and autonomy that is closely linked to the human genome and consider each of these separately when discussing the ethical implications of human genome and germline editing.

EMBO Reports (2018) 19: e46789