Ethical Considerations in Human Genome Editing:

Exploring CRISPR Technology through the Prism of Qawāʿid and Maqāṣid

Sayyed Mohamed Muhsin, Afiqah Fatunah binti Awang, Alexis Heng Boon Chin

(Sayyed Mohamed Muhsin is an Assistant Professor of Islamic jurisprudence at International Islamic University Malaysia, Afiqah Fatunah binti Awang is a Researcher at International Islamic University Malaysia, and Dr Alexis Heng Boon Chin, originally from Singapore, is an Associate Professor of Biomedical science at Peking University, China.)

Introduction

Rapid technological advances in the modern era have brought much benefit to human life in terms of facilitating various tasks, as well as improving healthcare in the medical field. Gene editing utilizing Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is one of the most promising newly-developed technology platforms within the genetic engineering field, with the potential to prevent and cure genetic diseases that can be transmitted from one generation to another [1, 2]. CRISPR is a Nobel Prize–winning technology, that has profound ethical and social implications, which in turn have attracted much attention from various sectors of society across the globe [3, 4]. Given that Islam is a major world religion with approximately two billion followers, how new medical technologies align with Islamic principles is important to these two billion people, which will in turn have a major impact on the uptake of new technologies such as CRISPR worldwide and their commercial success.

Gene editing can be performed on both somatic cells and germline cells to change a person’s traits through DNA, which is achieved by removing or altering a particular gene sequence in one’s DNA. To date, CRISPR/Cas9-based gene editing has been used to prevent a diverse array of genetic diseases including Chronic Granulomatous disease, β-thalassaemia, cystic fibrosis, haemophilia A, and Duchene Muscular Dystrophy [14].

A few years ago, Chinese scientist Dr. He Jiankui utilised CRISPR/cas9 technology to create gene-edited HIV-resistant twins from a parent that was HIV-positive, which was highly controversial, and ended up in a jail sentence for the scientist involved. Even though this case seems to be particularly beneficial to the patient and his offspring, there are serious ethical violations pertaining to the efficacy and safety of the technique, which has aroused intensive debates on the potential abuse of this new technology platform. Regarding the HIV gene editing case, this experiment was performed without any ethical approval and regulatory oversight from the pertinent health authority. Moreover, the prospective parents have not been properly counselled and given detailed information about the risks of this experiment, which could potentially have negative effects on the offspring [19]. This issue has caught the world’s attention since there are few countries that have prohibited the application of genetic modification technology in curing diseases and modifying human traits [20]. Genetic manipulation can lead to the birth of genetically-enhanced designer babies that may lead to various social issues related to discrimination and inequality in society. Therefore, international biomedical ethics boards and committees must promulgate rigorous and comprehensive guidelines to prevent the abuse of gene editing technology.

Islamic jurisprudence (fiqh) puts forth certain blueprints for evaluating and selecting the optimal course of action when faced with conflicting benefits and harms. This framework is particularly relevant when extrapolating resolutions in the context of involving potential public health benefits and major ethical and practical threats to health equity. For example, among the five Islamic legal maxims (al-qawāʿid al-fiqhiyyah) which reflect the objectives (maqāṣid)of the Sharīʿah, the maxim ‘harm must be eliminated’ is directly related to medical treatment as it works for removing a person’s mental and physical harm. CRISPR is a revolutionising invention in preventing and treating diseases in a “cheaper, faster, more powerful, and easier” method. In that sense, CRISPR is a powerful tool for implementing al-qawāʿid al-fiqhiyyah related to the elimination of harm [5, 6, 7]. However, this maxim is regulated with certain sub-maxims which include “repelling evils is preferable over attaining benefits,” “harm is not repelled by another harm,” “the greater harm should be prevented by forbearing the lesser harm,” and “personal injury should be tolerated to prevent general injury.” These maxims (qawāʿid) set forth the parameters that directly pertain to the use of CRISPR for medical use, especially under the shadow of doubts vis-a-vis the equity of public health and underrepresented communities in society and the potential abuse surrounding it [22].

Within the Muslim world, the current controversy over gene editing has also aroused much concern among many Islamic scholars, who have to critically examine this issue from the lens of the Sharīʿah [5, 6, 7]. While gene editing technology certainly has the potential of curing or preventing various chronic diseases, it also raises ethical dilemmas regarding the potential abuse of this new technology platform. In general, Islam encourages its adherents to seek cure and medicine when they are afflicted with pain or diseases but within the conditions and guidelines specified by Sharīʿah, such as not causing harm to oneself and other people, and the need for proven efficacy in medical treatment. Hence, there is a dire need to critically examine CRISPR/cas9 ethical issues from the Sharīʿah perspective and propose guidelines that are in line with the objective of the Sharīʿah (maqāṣid al-Sharīʿah). Therefore, the primary objective here is to analyse CRISPR-based gene editing technology through the lens of qawāʿid and maqāṣid in order to underscore specific ethical insights.

International Ethical Perspectives on CRISPR-based Gene Editing Technology

Ethical discussions regarding the permissibility of using CRISPR-based gene editing technology are divided into two opposing camps; those who support it and those who disagree. Proponents of CRISPR technology view its usefulness in curing chronic illness and consider it unethical to stop this technology from benefiting patients. On the other hand, opponents of this technology view it in terms of its effect and implications for the offspring, which has triggered much concern among researchers. For instance, the birth of the HIV-resistant Chinese twins achieved by Dr. He Jiankui has sparked more questions regarding the validation of the safety and efficacy of this new technology platform.

Moreover, the application of CRISPR-Cas9 can potentially cause genetic mutations such as mosaicism in the baby, which can result in other new, undiagnosed defects in germline cells that can only be identified after birth. Besides safety and efficacy, there are also other ethical dilemmas on the potential abuse of gene editing technology for other purposes such as altering human traits that are not related to diseases, such as intelligence, height, and complexion. The best way to address this issue is to have regulations at the international level. Furthermore, patients should undergo thorough counselling to gain a clear understanding of the potential risks and outcomes, both positive and negative, associated with the procedure. This knowledge is crucial as they will ultimately be responsible for the consequences if they choose to proceed. To date, the World Health Organization (WHO) has issued new recommendations on human genome editing for the advancement of public health with an emphasis on safety, effectiveness, and ethics [15]. 

CRISPR Technology Through the Prism of Qawāʿid and Maqāṣid

Islam does not prohibit Muslims from seeking medical treatment and using medicine for their illnesses. In fact, Muslims are encouraged to pursue healthcare as long as the treatments adhere to Sharīʿah principles and ethics. Gene editing is a modern-day issue, and within the Qurʾān and ḥadīt̲h̲, direct reading regarding its permissibility or prohibition may not be readily found. However, scholars can extrapolate from them guidance and direction indirectly, akin to their approach in resolving other contemporary matters. Scholars must address this issue through independent legal reasoning (ijtihād), which entails engaging in independent and original interpretations of matters not explicitly addressed in the Qurʾān, ḥadīt̲h̲, or scholarly consensus (ijmāʿ). This process necessitates drawing upon the core principles and values of Islam concerning the issue, such as the sanctity of human life, the avoidance of harm, and reverence for divine creation [21]. In line with overarching Islamic principles, ijtihād can be guided and governed by the use of al-qawāʿid al-fiqhiyyah as effective tools, with maqāṣid al-Sharīʿah serving as ultimate goals. Al-qawāʿid al-fiqhiyyah provide Muslim jurists with the means to apply and adapt legal reasoning to contemporary issues. Maqāṣid al-Sharīʿah encompass the broader aims and objectives of Islamic law, representing its philosophical foundation. They focus on safeguarding five key elements, namely religion, life, lineage, wealth, and intellect, ultimately contributing to success in both this world and the hereafter (ḥasanah fi l-dunya wa ḥasanah fī-l-ākhirah).

The five universal legal qawāʿid in Islamic jurisprudence are (1) ‘matters are judged by their objectives (intention),’ (2) ‘certainty cannot be overruled by doubt,’ (3) ‘hardship begets facility,’ (4) ‘harm must be eliminated,’ and (5) ‘custom is authoritative.’ Firstly, the construct of the intention (niyyah) of using new medical technology such as gene editing must be for beneficial purposes, such as the treatment and prevention of serious illness, and not to produce a designer baby. CRISPR technology is permissible when it is solely employed for the treatment of diseases or serious illnesses. It has to be used for medical purposes, specifically in the prevention of hereditary diseases and their treatment. However, it is absolutely prohibited to utilize CRISPR technology for cosmetic purposes.

Secondly, the use of CRISPR technology should only take place after meticulous assessment and under the vigilant supervision of the relevant national legal and medical authorities. This technology’s safety and functionality must be confirmed and verified by the relevant authorities according to the construct of certainty (yaqīn). In addition, the long-term effects of CRISPR on health equity and the human body needs to be studied considering the ethical and real-world implications, which are also underlined by the construct of yaqīn [16].

Thirdly, the use of CRISPR technology should align with the construct of harm (ḍarar), which is to eliminate harm or injury to the patient and the community. All the possible outcomes of CRISPR must be informed to the patient and confirmed by medical experts. In addition, the abovementioned types of harm to public health and minority groups need to be dealt with extreme care because, from an Islamic perspective, individual benefits need to be compromised for promoting public benefits. This aspect needs to be highlighted as “neither the APHA’s Health Equity Fact Sheets nor the AMA’s Health Equity Strategic Plan presently address issues of equity and inclusion in genomic medicine” [22].

Next, all possible treatment alternatives must be considered, unless the patient is in desperate condition and there is no option. CRISPR is then allowed to be performed based on the construct of necessity (ḍarūrah). Lastly, new medical technology must take into account local concerns and social context to explain the risk and advantages for the community, which is postulated by the construct of custom (ʿurf). Therefore, according to Islamic principles, technology that does not involve the transmission of altered traits to the next generation is allowed otherwise it is forbidden.

From a maqāṣid perspective, every action should, in one way or another, aim for the fulfilment and advancement of the preservation of religion (ḥifẓ al-dīn), life (ḥifẓ al-nafs), offspring (ḥifẓ al-nasl), intellect (ḥifẓ al-ʿaql), wealth (ḥifẓ al-māl), and dignity (ḥifẓ al-ʿird) at both the individual and societal levels. Importantly, it should refrain from causing harm to any of these six interests mentioned above.

 Ḥifẓ al-dīn means to safeguard and reinforce the faith of each individual Muslim, shielding it from any influences that could distort their beliefs and lead them astray or compromise their behaviour [17]. Indeed, it also involves the cultivation of individuals with exemplary character, a positive outlook, compassion, and strong moral values. Creating a society characterized by wisdom, goodness, dignity, virtue, justice, responsibility, accountability, respect, and care is an integral aspect of ḥifẓ al-dīn on a broader societal scale [17]. If CRISPR technology is utilized to rectify physical or genetic impairments in an individual, enabling them to thrive, while at the same time advancing scientific knowledge, and contributing positively to humanity, it can thus be considered a means of enhancing one's faith and devotion, bringing them closer to Allah. This would thus align with the principle of ḥifẓ al-dīn. Numerous verses in the Qurʾān and ḥadīt̲hs have implored mankind to develop medical treatment for various human diseases, with biomedical research being seen as a highly virtuous act. In that light, the application of CRISPR technology for treating human diseases can thus be viewed as compliant with ḥifẓ al-dīn.

Ḥifẓ al-nafs encompasses the paramount duty of safeguarding human life from the various hazards that may threaten an individual's physical well-being, while also providing guidelines for upholding and promoting humane values. Among others, it involves recognizing access to healthcare as a fundamental human right; therefore, the deliberate denial of treatment constitutes a direct harm to one's very life [18]. It includes protection from acts such as sexual abuse, physical assault resulting in injuries or harm to the body's organs, acts of maiming, murder, or coercion leading to self-harm. Humaneness is a pivotal aspect of life that requires constant refinement and elevation. Ḥifẓ al-nafs opposes altering an individual's primordial human nature (fiṭrah), destabilizing the equilibrium of life, straying from life's fundamental objectives, constraining freedom, and similar infringements. CRISPR technology can thus be aligned with ḥifẓ al-nafs by being utilized for preserving and enhancing human life via treatment of various genetic diseases such as amyotrophic lateral sclerosis and cystic fibrosis, infectious diseases such as HIV, as well as cancer [3, 4]. Nevertheless, it must be noted that utilization of CRISPR technology for medical therapy is not without potential risks, which include incorrect on- versus off-target cleavage, and insufficient editing that can result in mosaicism [3, 4]. It is imperative that these risks be carefully considered, avoided, and prevented.

Ḥifẓ al-nasl refers to the protection of human offspring, ensuring human procreation and reproduction and safeguarding it from cessation. It starts from the pre-natal stage of existence. Part of it is protection of the notions of filiation (bunuwwah), motherhood (umūmah) and fatherhood (ubuwwah), based on natural cosmic laws and time-honoured moral values and social norms. Its objective is to nurture and promote the innate, natural feelings of love between parents and children. It encompasses ḥifẓ al-nasl and the sense of identity of future generations through the regulation of marriage and the establishment of strong family institutions [17]. Although CRISPR technology can be aligned with ḥifẓ al-nasl by curing or preventing known genetic diseases in one’s offspring [3, 4], there is a risk that consequent alteration of the human germline may adversely affect future generations. To date, there is a lack of reliable data to enable accurate evaluation of the potential risks of applying the newly-developed CRISPR technology on human patients [8]. Hence, current debate on the therapeutic applications of CRISPR technology is dominated by controversy over the potential safety risks of germline gene-editing techniques, which include unwanted changes in DNA sequence or structure at undesired locations, or mosaicism when gene editing occurs in some cells but not in others [9]. Provided that the safety and effectiveness of CRISPR technology in preventing or curing the transmission of inheritable genetic defects from parent to child can be validated in the future; this will thus be compliant with preserving one’s lineage (nasab) by ensuring the life and health of one’s progenies.

The human intellect serves as the distinguishing factor that sets humanity apart from other creations, and it is the focal point of legal obligation (manāṭ al-taklīf). Additionally, it functions as a conduit for the genuine worship of the Lord, enabling sound decisions to promote benefits and mitigate harm effectively. Ḥifẓ al-ʿaql involves preserving one's intellect and shielding individuals from circumstances that could compromise their mental and intellectual well-being and soundness.For this purpose, gene-editing via application of CRISPR technology can be potentially used to cure various neurological disorders, thereby preventing harm to human intellect or mental faculties. These include Alzheimer’s disease [10], Huntington’s chorea [11], frontotemporal dementia and epilepsy [12].

In the concept of ḥifẓ al-māl, the Sharīʿah places paramount importance on the ḥifẓ al-māl and delineates numerous rules and regulations governing the acquisition and expenditure of wealth in ethical ways. Any transgressions against property, such as usurpation, cheating, and fraud, are regarded as detrimental to the well-being of one's wealth. Application of CRISPR technology in gene editing for curing diseases is compliant with ḥifẓ al-māl, because it is known to be more accurate, faster, less expensive, and more cost-efficient than other existing genome editing technologies [13].

For ḥifẓ al-ʿird, the Sharīʿah prohibits actions such as backbiting, defamation, mockery, obscene talk, and scandal, as they are all seen as attacks or threats to an individual's dignity. To ensure that this objective is met, gene-editing with CRISPR technology must strictly be restricted to curing known diseases and not for enhancing socially-desirable traits such as intelligence, height, and skin complexion. Because modifying God’s creation for non-medical purposes is not valid according to Sharīʿah and can be considered a violation of human dignity and tampering Allah’s creation (taghyīr khalq Allah) which is prohibited (Q 30:30, Q 4:119). Another strict prerequisite to preserve human dignity and honour is to ensure informed consent prior to medical application of this technology on patients [7].

Concluding Remarks

Hence, it can be seen that exploration via qawāʿid and maqāṣid, provides a logical, well-rounded, and comprehensive methodology for dissecting and analysing key bioethical issues relating to how new medical technologies can impact mankind at both the individual and societal level, resulting in conclusions and regulatory safeguards that concur with that proposed by secular bioethicists. To the ignorant and bigoted, the analysis of bioethical issues based on Islamic religious principles is completely illogical and based on mere superstition. Nothing can be further from the truth. In fact, during the medieval era, it was Islamic scholars that pioneered the modern scientific method based on logical reasoning with such principles.

The majority of historians attribute development of the modern scientific method to the Muslim scientist al-Haytham [23], who is widely regarded as the father of modern optical science. His pioneering work changed the meaning of the term ‘optics,’ and established experiments as the norm of proof in the field. His investigations were based not on abstract theories, but on experimental evidences. His experiments were systematic and repeatable [23]. Indeed, the golden age of Islam prior to the Mongol invasion of Baghdad was characterized by rapid advancements in mathematics and science, as attested by modern scientific terminologies such as ‘Algebra’ and ‘Algorithm’ being of Arabic origin. In a similar light, logical reasoning based on that expounded by qawāʿid and maqāṣid can also serve as a foundational bedrock of modern and emerging bioethics.

By critically examining ethical concerns in the application of CRISPR technology in human genome editing through the prism of qawāʿid and maqāṣid, the following conclusions can thus be reached, which align with those articulated by secular bioethicists:

1. Before clinical applications on human patients, it’s safety and efficacy must be rigorously and comprehensively evaluated with in vitro laboratory assessments, as well as with in vivo animal testing. In the case of germline gene editing, particular care must be exercised to ensure that application of this new technology should not result in more harm to the parents, their offspring, and future generations.
2. Its use must be strictly restricted to medical purposes only, for the treatment and cure of known human diseases; while it’s use for enhancing socially-desirable traits such as intelligence, height and skin complexion should be prohibited, as this would be tampering with Allah’s creation.
3. There must be strict guidelines to ensure informed consent by patients, prior to undergoing medical therapy with this new technology. Ideally, patients should undergo counselling by a certified professional genetic counsellor before the signing of consent forms.

References

1. Segers S. Heritable genome editing: ethical aspects of a developing domain. Hum Reprod. 2023 Aug 15:dead167. DOI: 10.1093/humrep/dead167. Online ahead of print.
2. Alex K, Winkler EC. Comparative ethical evaluation of epigenome editing and genome editing in medicine: first steps and future directions. J Med Ethics. 2023 Aug 1:jme-2022-108888. DOI: 10.1136/jme-2022-108888. Online ahead of print.
3. Sauvagère S, Siatka C. CRISPR-Cas: 'The Multipurpose Molecular Tool' for Gene Therapy and Diagnosis. Genes (Basel). 2023 Jul 27; 14(8):1542.
4. Zheng R, Zhang L, Parvin R, Su L, Chi J, Shi K, Ye F, Huang X. Progress and Perspective of CRISPR-Cas9 Technology in Translational Medicine. Adv Sci (Weinh). 2023 Sep;10(25):e2300195.
5. Al-Balas QAE, Dajani R, Al-Delaimy WK. The Ethics of Gene Editing from an Islamic Perspective: A Focus on the Recent Gene Editing of the Chinese Twins. Sci Eng Ethics. 2020 Jun; 26(3):1851-1860.
6. Isa NM, Zulkifli NA, Man S. Islamic Perspectives on CRISPR/Cas9-Mediated Human Germline Gene Editing: A Preliminary Discussion. Sci Eng Ethics. 2020 Feb; 26(1): 309-323.
7. Alsomali N, Hussein G. CRISPR-Cas9 and He Jiankui's Case: an Islamic Bioethics Review using Maqasid al-Shari'a and Qawaid Fighiyyah. Asian Bioeth Rev. 2021 Mar 20;13(2):149-165. DOI: 10.1007/s41649-021-00167-1.
8. Brokowski, Carolyn, and Mazhar Adli. 2019. CRISPR ethics: moral considerations for applications of a powerful tool. Journal of Molecular Biology 431 (1): 88–101. DOI: 10.1016/j.jmb.2018.05.044.
9. Schaefer, Kellie A., Wen-Hsuan Wu, Diana F. Colgan, Stephen H. Tsang, Alexander G. Bassuk, and Vinit B. Mahajan. 2017. Unexpected mutations after CRISPR–Cas9 editing in vivo. Nature Methods 14 (6): 547–548. DOI: 10.1038/nmeth.4293.
10. Lu L, Yu X, Cai Y, Sun M, Yang H. Application of CRISPR/Cas9 in Alzheimer's Disease. Front Neurosci. 2021 Dec 21; 15:803894.
11. Alkanli SS, Alkanli N, Ay A, Albeniz I. CRISPR/Cas9 Mediated Therapeutic Approach in Huntington's Disease. Mol Neurobiol. 2023 Mar; 60(3):1486-1498.
12. Guan L, Han Y, Yang C, Lu S, Du J, Li H, Lin J. CRISPR-Cas9-Mediated Gene Therapy in Neurological Disorders. Mol Neurobiol. 2022 Feb; 59(2):968-982.
13. Cox, David Benjamin Turitz, Randall Jeffrey Platt, and Feng Zhang. 2015. Therapeutic genome editing: prospects and challenges. Nature Medicine. 21 (2): 121. DOI: 10.1038/nm.3793.
14. Yusof, W. (2017) ‘CRISPR/Cas9: An Introduction to Genome Editing’. Malaysian Journal of Paediatrics and Child Health, 23(1):10.
15. World Health Organization, (n,d), WHO issues new recommendations on human genome editing for the Advancement of Public Health, Accessed on 13 May 2023 from: https://www.who.int/news/item/12-07-2021-who-issues-new-recommendations-on-human-genome-editing-for-the-advancement-of-public-health.
16. Andrew M. Subica, “CRISPR in Public Health: The Health Equity Implications and Role of Community in Gene-Editing Research and Applications,” American Journal of Public Health , no. (): pp. e1-e9. DOI: 10.2105/AJPH.2023.307315.
17. Mohamed El-Tahir El-Mesawi, Waleed Fekry Faris & Dawood A. Yahya Al-Hidabi, Regrounding Maqāṣid al-Sharīʿah: The Quranic Semantics of Human and Foundation of Human Common Good (Kuala Lumpur: International Institute for Muslim Unity (IIMU), 2022).
18. ʿAbd al-Majīd al-Najjār, Maqāṣid al-Sharīʿah bi Abʿādin Jadīdah (Beirut: Dār al-Gharb al-Islāmī, 2nd edn., 2008).
19. Chen Q, Ma Y, Labude M, Schaefer GO, Xafis V, Mills P. Making sense of it all: Ethical reflections on the conditions surrounding the first genome-edited babies. Wellcome Open Res. 2021 Jun 23; 5:216.
20. Zheng R, Zhang L, Parvin R, Su L, Chi J, Shi K, Ye F, Huang X. Progress and Perspective of CRISPR-Cas9 Technology in Translational Medicine. Adv Sci (Weinh). 2023 Sep; 10(25):e2300195.
21. International Islamic Fiqh Academy, (2013), ‘Resolution on Genetics, Genetic Engineering and the Human Genome (Genome)’ No: 203, (21/9), Accessed from: https://iifa-aifi.org/2416.html on 13 May 2023.
22. Subica AM. CRISPR in Public Health: The Health Equity Implications and Role of Community in Gene-Editing Research and Applications. Am J Public Health. 2023 Aug;113(8):874-882. DOI: 10.2105/AJPH.2023.307315.
23. Gorini R. Al-Haytham the man of experience: First Steps in the Science of Vision. J Inter Soc for the History of Islamic Medicine (JISHIM) 2003; 2(4):53–55. [Google Scholar]