Pulse
4 December 2023
In November 2018, media across the world is abuzz with the news of the birth of two girls whose genes have been modified to make them immune from HIV. He Jiankui, a scientist from China, and his team, managed to disable the CCR5 gene that triggers the HIV infection.
The outcry surrounding the scientists’ use of human embryos, which were brought to life birth, for this experiment need not detain us. There are numerous media articles and academic papers that discuss the ethics of experiments of this nature, which, according to guidelines published by the National Health Commission in 2003, is clearly banned in China.
Of particular interest of us in this article is the new technology that the scientists used to accomplish this, namely, CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9). To date, CRISPR is the most versatile genomic engineering tool created in the history of molecular technology.
Barely one decade old, the CRISPR system has shown remarkable promise for what have described as an ‘infinite’ number of applications. Compared to other older gene editing techniques such as zinc finger nucleases (ZFN) and transcription activators like effector nucleases (TALENs), CRISPR technology is superior because it is faster, cheaper and more accurate.
CRISPR can be used in many areas such as agriculture and pest control. In addition, CRISPR could revolutionise basic science by giving scientists further or new insights on gene, organisms and animals. As Carolyn Brokowski and Mazhar Adli put it:
From viruses and bacteria, to simple model organisms, such as Drosophila melanogaster (fruit fly), Anopheles gambiae (mosquito), Saccharomyces cerevisiae (budding yeast), Hydra magnipapillata (hydra), Caenorhabditis elegans (round worm), Danio rerio (zebra fish), and Arabidopsis thaliana (rockcress), to larger animals such as pigs, cattle, and monkeys and even human zygotes, CRISPR experimentation has led to novel, important findings.
However, it is the promise it holds in treating, curing or totally eradicating diseases in humans that is arguably most exciting, but also quite controversial. Scientists believe that CRISPR could possibly treat or even eradicate altogether serious diseases such as diabetes, Leber Disease, Sickle Cells Disease, Duchenne Muscular Dystrophy, and some cancers.
Scientists believe that CRISPR could also be used to eradicate certain diseases such as breast cancer by editing the genes of embryos or gametes such that the alterations would affect future generations. Known as ‘inheritable genetic modification’, some scientists believe that the use of this technique could serve the common good.
The use of CRISPR, however, is not limited only to therapeutic purposes. The technique can be used for enhancement, that is, to boost human capabilities beyond what is deemed to be the ‘species-typical level or statistically normal range of functioning.’ The technique could also be used to create ‘designer babies’, with ‘desirable’ traits such a blue eyes or enhanced intelligence.
To state that the more powerful the technology is the greater its dangers is something of a truism. But in the case of CRISPR, it is a truism that should not be ignored. In this article, we discuss briefly some of the ethical concerns surrounding this technology.
USING CRISPR FOR RESEARCH
There are several important theological, philosophical and ethical issues associated with using CRISPR for research. Space, however, allows us to discuss only the main issues.
Insofar as CRISPR is used to edit or manipulate the genes of human embryos, such research would present serious problems for Christians. This is because Christians are of the view that the human embryo – from the moment of conception – is the bearer of the image and likeness of God (Genesis 1:26-27). The human embryo must therefore be valued like all human beings, and its life and dignity must be protected.
CRISPR research that involves the creation, manipulation and subsequent destruction of the human embryo is therefore, for Christians, an unconscionable violation of human life. Such research should be prohibited even if its outcome may benefit society, such as the prevention or cure of certain diseases for which there is hitherto no effective treatment.
This is because Christian ethics rejects the logic that is espoused by some versions of secular ethics which states that the ends justify the means.
Caution must be exercised even if CRISPR is used in research where human embryos are not involved. This is because although CRISPR is superior to older techniques and technologies, it is not always as efficient as scientists hoped.
For example, CRISPR is not always efficient when it is used to repair cells. Sometimes, segments of DNA may be unintentionally deleted or rearranged. DNA bases from elsewhere may also be accidentally incorporated into the gene.
Besides these off-target effects (unwanted edits in the wrong places), there is also the problem of mosaicism. According to the Nuffield Council of Bioethics:
Mosaicism describes the situation in which not all cells of an individual are genetically identical but, instead, cells harbouring distinct mutations co-exist in the same organism.
In other words, there is the possibility that some cells would carry the edits while others would not.
According to Victor Lange and Klemens Kappel, mosaicism has been linked to dangerous conditions such as cancer. In addition, since mosaicism means that the edit of the disease-relevant gene is incomplete, there is still a possibility that the individual may develop the disease.
Thus, despite its evident efficiency and accuracy CRISPR still poses some risks that should not be ignored.
Scientists and ethicists alike are concerned about the possible creation of ecological disequilibrium once CRISPR is widely used. For example, the accumulative effect of off-target mutations caused by CRISPR may be detrimental not just for the individual organism but also for the entire species when these mutations – which can be very difficult to detect – are passed down to future generations.
The use of CRISPR to eliminate certain diseases such as dengue or Zika by rendering certain male mosquitoes infertile may wipe out the entire species altogether. This may have serious consequences to the ecological equilibrium which is difficult or even impossible to predict.
Furthermore, ethicists and scientists have also warned about the disastrous consequences to the ecology if novel organisms created in the laboratory using CRISPR are accidentally released in the environment and begin to replicate in such a way that it is impossible to monitor, much less control.
THERAPEUTIC AND NON-THERAPEUTIC USES
As we have seen, the use of CRISPR has the potential to treat, cure and prevent a variety of diseases. This can be done either by somatic therapies, which involve the editing of an individual’s non-reproductive cells, or by germline modifications. We will discuss the ethical issues associated with these approaches below.
However, the same technology and technique could also theoretically be used for non-therapeutic purposes – for example, to enhance certain human traits such as physical prowess, memory or intelligence. While many would no doubt support the use of gene-editing techniques for therapy, much fewer would be in favour of using it for non-therapeutic purposes such as the enhancement of certain traits.
Many bioethicists have argued that restrain must be exercised when it comes to using medical technology for non-therapeutic ends such as enhancements because they question that such practices are in line with the moral requirements of medicine. Others question whether enhancement does in fact serve the common good, the good of humans as humans.
In Biotechnology and the Human Good (2007), John F. Kilner and his co-authors argue that the culture of enhancement will radically and adversely distort the way in which we see both our selves and others. They write:
A powerful argument relevant to the cloning debate is equally applicable to the enhancement question. This is the repugnance, the intuitive feeling of disgust and revulsion, many experience over the overweening hubris of self-worship that enhancement fosters. On grounds of both secular and religious humanism, the gross obsession with one’s self (body and psyche) that motivates primary enhancement would be unseemly at best and pathological narcissism at worst.
While many will agree with this general assessment, the question that exercises the minds of ethicists is what counts as pathology. As Brokowski and Adli put it, answering the question of what constitutes treatment and what constitutes enhancement is ‘problematic because of the difficulty with deciding about what “counts” as pathology vs. what is merely a minor or even moderate deviation from the “norm” in a given context.’
Even the question of what is ‘normal’ (and who gets to define normalcy) is also being disputed.
Brokowski and Adli cite the hypothetical example of using gene-editing to correct bad-cholesterol level, stating that ‘Whether this hypothetical scenario, which may benefit both the individual and society in the long run, should be classified as enhancement or a medical need is unclear.’
Setting aside the somewhat ambiguous status of cholesterol adjustments, the ethics of even more obvious forms of enhancements such as increasing athletic performances and memory are still being debated, with no consensus in sight.
SOMATIC VERSUS GERMLINE EDITING
Another important consideration has to do with the kind of cells CRISPR is used to edit or modify. Some diseases can theoretically be treated by editing the genes of the non-reproductive cells of the body, a technique which is called somatic editing. However, scientists believe that certain diseases can only be treated by editing the reproductive cells or early embryos. This technique is called germline editing.
While somatic editing may raise some of the safety issues that we discussed above such as off-target mutations and mosaicism, ethicists generally are of the view that it poses less ethical concerns than germline editing.
The main concern with germline editing is that the modifications made by CRISPR could be transmitted to future generations. Thus, while somatic editing affects only the individual patient, germline editing can affect future generations in ways that are difficult to anticipate.
In addition, in somatic editing, the mutations are confined and their effects are evident only the cells in which they occur. However, in germline editing, the mutations are not only often ‘silent’ and difficult to detect in the parent organism and manifest only at a later stage.
As E. Rodriguez explains,
In general, therapeutic genome editing interventions in somatic cells is ethically accepted, considering the balance between risks and benefits and the use of informed consent. But germline cells are not the same, since the CRISPR/Cas9 technique can produce mutations and side effects, unpredictable changes may be transmitted to future generations.
Christian ethics is concerned not just with the consequences that the present generation may face due to certain actions and initiatives. It is also profoundly concerned with the impact that the decisions and actions of the current generation might have for the next.
Thus, the Christian idea of our moral obligation to one another includes future generations as well. As the renowned bioethicist and Catholic intellectual, Daniel Callahan, has argued in an article published in 1981, to exclude any human being – present or future – from our moral consideration is to be complicit to some form of oppression.
In fact, Christian theologians such as Donald M. MacKay have even argued that Jesus’ command to love one’s neighbour (Luke 10) extends to the future generations to the degree that our current actions may benefit (or harm) them.
These moral concerns do not perplex only Christians. Already in 1997 UNESCO issued a Universal Declaration on the Human Genome and Human rights which recommended a global moratorium for any kind of technological intervention on the human germline, including gene editing.
In December 2015, the International Summit on Human Gene Editing – a gathering of the scientific academies of America, Britain and China agreed that the altering of gametocytes and early embryos to generate inheritable changes is irresponsible.
However, not all jurisdictions have taken this ethically responsible approach. Not unexpectedly, in February 2016, UK regulators have given British scientists permission to use CRISPR to edit the genes of embryos, but specify that this should be done only in the context of research.
JUSTICE ISSUES
Finally, and very briefly, CRISPR exacerbates issues of justice which are already present in other forms of genetic engineering and in medicine generally.
The first consideration has to do with what may be described as procedural justice, which concerns the process by which decisions are made and who gets to make them. Procedural justice also concerns the influence that stakeholders have on these decisions, matters related to transparency and accountability.
The second cluster of justice-related issues can be described as issues of distributive justice. Here the concern is whether there is fair distribution of the benefits and burdens based on the decisions and policies concerning CRISPR gene-therapy.
The most obvious question with regard to the fair distribution of the benefits of CRISPR related gene-editing technology is who can have access to it. Like many if not all novel biomedical advancements, CRISPR applications are expected to be profitable for patent holders. This means that CRISPR-based products are very likely to be costly.
Consequently, as Brokowski and Adli point out: ‘… an ethical question is whether the high price-tag will make CRISPR product available only to the world’s elites.’ They add:
Since much of the funding for CRISPR characterisation and development was provided by grants from government funds and thus taxpayers’ money, it is morally problematic to deny potentially lifesaving benefits of the technology to the very individuals who funded much of its development in the first place.
Even if the costs of CRISPR related therapies are within the reach of the majority of the population, some may still have to make difficult decisions about what necessities they have to forgo in order to get treatment.
‘For instance,’ write Brokowski and Adli, ‘those needing CRISPR-based applications to maintain a reasonable quality of life, or even life itself, might be forced to make painful economic choices about whether to spend funds on therapeutics, food, or other essential living necessities.’
CONCLUSION
In the Epilogue of her insightful book entitled Altered Inheritance: CRISPR and the Ethics of Human Genome Editing, Françoise Baylis of Dalhousie University, Canada, reflects on the broader question of the implications of genome editing on the common good and indeed in shaping our future world.
She sketches her hope of the future thus:
I have already described the world that I want to live in – a world that promotes equity and justice, and celebrates differences; a world that embraces neighbourliness, reciprocity, social solidarity, and community; and a world that values collegial as opposed to competitive relations. In this imagined future world, our social, relational, interdependent selves rise above our individualistic, competitive selves, and we all flourish as we pursue the goal of building a better world for us all.
Then she adds poignantly:
If this is the kind of world you might also want to live in, then I invite you to think carefully about whether, and if so how, heritable human genome editing can help us to build this world. If, for example, this technology can help reduce inequity, then we have a responsibility to ensure that it is directed in a way as to promote justice and fairness. But if it has no hope of addressing this challenge, then we must seriously weigh the opportunity costs in continuing to invest time, talent, and treasure in developing heritable human editing technology, when these same resources could more usefully be spent on other valuable research that aims to improve the human condition and the world in which we live.
She ends her book with these words: ‘May [the decisions we make] be characterised by wisdom and benevolence. And, may we never lose sight of our responsibilities to “us all”’.
May the scientific community, policy makers, entrepreneurs and all stakeholders who are involved in this emerging new technology of genome editing take heed of Baylis’ wise exhortation.
Dr Roland Chia is Chew Hock Hin Professor at Trinity Theological College (Singapore) and Theological and Research Advisor of the Ethos Institute for Public Christianity.