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COMMENT

Starting the conversation: CRISPR’s role in India

Farhad Udwadia, Shivam Singh

Published online: April 18, 2019

DOI: 10.20529/IJME.2019.016


Abstract

The applications of gene editing technologies such as CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) have grown significantly in recent years. Several countries have adopted different stances on the regulation of such technology; however, India does not have any legally enforceable regulations in place. There is a need for such a development as India’s regulatory, sociocultural, and economic landscape is unique. First, we discuss the uncertainty regarding India’s regulatory capacity to enforce ethical standards for CRISPR use. Then, we discuss unique driving forces that could lead to the misuse of CRISPR in India, such as certain sociocultural norms like preferences for fair skin and public demand for sex determination. Given these previous concerns, we posit the question; where on the priority list does CRISPR stand in the context of public health in India?

Perspective

Late in 2018, the world stood by in disbelief as a Chinese scientist reportedly created two genetically engineered human beings using CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) gene-editing technology (1). This development, which had been merely a challenging possibility not so long ago, has led to the resurgence of a host of ethical questions in the scientific community regarding the use of CRISPR, such as those involving off-target effects, access, and regulation (2). On a global front, the technology has been growing faster than our ability to reach any sort of moral consensus on its use and regulation. The successful genetic modification of human embryos, and now, human beings, has fueled apprehensions that this technology could one day be used to design and pick babies with certain designer character traits. Would it be ethical for parents to customise a baby that could run like Usain Bolt and sing like Beyoncé? While experts discredit these specific applications as being unlikely in the near future, the ability to control far less complex and highly heritable traits, such as skin color and gender, are not (3).

Currently, there are no internationally agreed-upon laws or regulations on gene editing, leaving scientific research and application of CRISPR technology to the discretion of individual countries (4). Although some countries, like the United States, the United Kingdom, Canada, and Germany, have strict rules prohibiting genetic modification of the human germ line either experimentally or clinically, other countries like France and Argentina are not as clearly regulated (4, 5). It was only last year that Japan set specific guidelines for the use of CRISPR technology to move towards furthering research on gene-editing in early human embryo development (6). As it stands, Indian protocols prohibit human germ line editing and reproductive cloning, as detailed in the National Guidelines for Stem Cell Research by the Indian Council of Medical Research. However, the concern is that these guidelines have not yet been converted into specific laws (7, 8). This concern was highlighted a few years ago by the Japanese bioethicist Tetsuya Ishii, who noted that some countries, such as China, Japan, and India, ban genomic editing for clinical use, and yet these bans are not legally binding and are seen as unenforceable because of the large population and lack of specific criminal laws to act as a deterrent (5). This, coupled with factors such as the availability of do-it-yourself CRISPR kits and the huge number of commercial fertility clinics, has raised red flags because of the potential for misuse and manipulation (5, 9).

Based on the management of scientific technology in the past, it is uncertain whether or not the current regulatory landscape in India would be capable of enforcing the regulation of such an immensely powerful technology in a safe and ethical manner. Past developments in genetic technology have been mishandled, demonstrating the capacity (or lack thereof) of India’s regulatory organisations. For example, take the development of genetically modified crops. While the permissibility of these was still being debated in parliament, they were being illegally and prematurely sown in Gujarat in spades because of their perceived profitability (10). This was largely a result of corrupt practices in Indian regulatory agencies. In the medical field, India has even gone so far as to ban the clinical use of stem cell therapy because of “rampant malpractice” and the inability to regulate its commercial use (7). Corruption within such organisations is so rampant that India’s medical administration is said to be one of the most corrupt in the world, with physicians, medical regulatory bodies, and even the government playing a part (11).

The Medical Council of India (MCI) and the Indian Medical Association (IMA) have faced numerous scandals regarding bribes for the establishment of ventures and even entire institutions. Efforts to hold them accountable through the legal systems have been null and void because of the backlog of cases, and only a small fraction of prosecutions have resulted in legal consequences (11). Therefore, there is little discouragement of the misuse and manipulation of medical technology for personal or commercial gain. The extensive growth of black markets for human organs and counterfeit medicine in India is the greatest testament to this statement. India’s black market for organs is one of the largest in the world, with hospital administrators, doctors, and even law enforcement officials regularly caught for the procurement and sale of black market organs (12). This paints an alarming picture of the state of regulation with regard to medical services in India, and raises several concerns when considering the regulation of profitable gene-editing technology.

Translating these discussions into public discourse is urgent, as advances in gene-editing technology have already begun to gather momentum. Private companies have already sought to explore the commercial potential of such technology in India and they will surely march forward in due time (10). On a more positive note, Indian scientists have been making remarkable advancements in research using gene-editing technology, which involves manipulating somatic cell samples from patients with blood disorders like sickle-cell anemia (9). The key question at hand is whether or not research will continue to be conducted in a safe and ethical manner, and this seems doubtful without legally enforceable guidelines and an effective regulatory and legal infrastructure.

The potential for misuse in an Indian context is driven by a number of sociocultural factors intrinsic to the subcontinent. For example, take the all too familiar preference for fair skin in Indian society. The pervasiveness of general concern over skin color is reflected in consumer markets, with the Indian population having spent over $500 million on “fairness” products in 2014 (13). This sociocultural obsession translates into discrimination against darker skin tones in the professional sphere. In 2012, close to 70% of the surveyed population preferred partners of a fairer complexion, and furthermore, many industries, including the film, hospitality, and aviation industries, are marred by cases of active discrimination against applicants with darker complexions (14, 15). To what extent will these preferences take form in healthcare markets if consumers are able to manipulate such characteristics? The demand for these traits definitely exists, and it would not be unreasonable to be concerned over potential future misuse of technologies like CRISPR to meet such a demand.

Perhaps the sociocultural element that merits the greatest consideration is one that the Indian medical profession has been grappling with for centuries. The preference for a male child is behind some of the most severe ethical breaches among the medical profession. In fact, fairly recent technological advances have been shown to empower such preferences, contributing to the vastly skewed sex ratios observed in many Indian states (16). The normal sex ratio observed for children is 952 girls per 1000 boys, yet in states such as Haryana it remains as low as 830:1000, and states like Punjab, Delhi, Bihar, Gujarat, Andhra Pradesh, and Madhya Pradesh all fall significantly short of the normal (17). According to public health scholars, the increased availability of ultrasound machines in rural areas coupled with poor to no regulation of sex determination laws is one of the driving factors behind these skewed ratios (18). This is a worrisome trend that results in adverse effects to the Indian population as a whole, the effects of which have been extensively studied. From an economic perspective, according to a report by McKinsey & Co, India’s GDP could be 60% higher in 2025 if women played the same role in the workforce as men (19). While there is no doubt that other factors (sexism in the work force, systemic patriarchy, etc.) also contribute to an unequal workforce, skewed sex ratios are not an insignificant driving factor. From a social standpoint, empirical studies have also linked skewed sex ratios to the increase in violent sexual crimes, specifically human trafficking and sexual abuse (19). Therefore, we see that we have a moral and economic imperative to safeguard these ratios and prevent unlawful sex selection. Current trends foreshadow the potential for future misuse and misapplication, and the way medical technology has been misused in the past can serve as important lessons. If past and existing medical technologies have been misused because of these driving sociocultural factors, it gives us reason to believe that this could be the case with gene-editing technology as well. Therefore, the efficacious and ethical regulation of CRISPR technology must take these factors into consideration.

Finally, given the unique sociocultural, economic, and regulatory landscape of India, we must also ask to what degree we are willing to allocate resources towards the development and application of technologies like CRISPR. Furthermore, to what extent might gene-editing technology worsen pre-existing injustice and inequality? It is unlikely that the substantial proportion of Indians who live in poverty‒363 million to be exact‒would be the direct beneficiaries of CRISPR (20). In a country where the top 1% is responsible for 73% of the country’s wealth and 60% of women do not have access to hospital care when giving birth, can we justify further reallocating valuable and limited resources that will likely benefit only the wealthy few? (21, 22). Should we also not be even more cautious if this technology could one day lead to cognitive or physical genetic enhancement for its beneficiaries? As the Western world gears up to allocate resources towards the development and application of CRISPR technology, we feel developing countries like India must be cautious. A technology should have an evidenced and favorable risk/benefit ratio in order to justify a higher prioritisation of resources. Approximately 423,000 Indians die from tuberculosis, 205,000 die from malaria and 105,000 die from diarrhoea each year, to name only a few diseases (2325). Interventions that are effective and cost effective exist, and we feel these should take priority.

The promises of gene-editing technologies are discussed and disseminated to a great degree, and with good reason. They represent very real, tangible opportunities at positively impacting the lives of certain patients with certain diseases. However, it is important not to generalise this potential across societies and nations, but to recognise that each country is unique and has its own narrative. The sociocultural factors discussed above have been woven into medical practice in India for decades, despite the best attempts at regulation. Going forward, understanding that this technology, with such great potential for unethical use, requires more caution than optimism, regulatory efforts must pause to consider these issues in depth.

If India is to pursue advancements in gene-editing technology, it is important that they do not follow the laws of other countries; rather, it is crucial that rules and regulations are created to take into account India’s unique professional and sociocultural landscape and, in addition, its capacity for ensuring that such a technology is handled responsibly and ethically.

References

  1. Belluz J. Is the CRISPR baby controversy the start of a terrifying new chapter in gene editing? Vox.com. 2018 Dec 3 [cited 2019 Mar 30]. Available from: http://www.vox.com/science-and-health/2018/11/30/18119589/crispr-technology-he-jiankui
  2. Brokowski C, Adli M. CRISPR Ethics: Moral Considerations for Applications of a Powerful Tool. J Mol Biol. 2019 Jan 4;431(1):88-101. doi: 10.1016/j.jmb.2018.05.044
  3. Adashi EY, Cohen IG. The Ethics of Heritable Genome Editing: New Considerations in a Controversial Area. JAMA. 2018;320(24):2531–2
  4. Vogel KM. Crispr Goes Global: A Snapshot of Rules, Policies, and Attitudes. Bull At Sci. 2018 June 5[cited 2019 Mar 30]. Available from: thebulletin.org/2018/06/crispr-goes-global-a-snapshot-of-rules-policies-and-attitudes/?fbclid=IwAR3-0mnLFEag9bRgjXSliNqeih9LDvKrwoym2-zLzQO3BLr87X2lqKAas9g
  5. Ledford H. Where in the World Could the First CRISPR Baby Be Born? Nature News. 2015 Oct 13[cited 2019 Mar 29]. Available from: www.nature.com/news/where-in-the-world-could-the-first-crispr-baby-be-born-1.18542
  6. Cyranoski D. Japan set to allow gene editing in human embryos. Nature. 2018 Oct 3 [cited 2019 Mar 29]. Available from: https://www.nature.com/articles/d41586-018-06847-7
  7. Jayaraman KS. India bans commercial use of stem cells for therapy. Nature India. 2017 Oct 15 [cited Mar 31]. Available from:www.natureasia.com/en/nindia/article/10.1038/nindia.2017.130
  8. Indian Council of Medical Research. National Ethical Guidelines for Biomedical Research Involving Human Participants. New Delhi: ICMR; 2017 Oct[cited 2019 Mar 29]. Available from: http://icmr.nic.in/sites/default/files/guidelines/ICMR_Ethical_Guidelines_2017.pdf
  9. Priyadarshini S. Armed with CRISPR scissors, Indian scientists look at curing the incurable. Nature India. 2018 Aug 7[cited 2019 Mar 31]. Available from: https://www.natureasia.com/en/nindia/article/10.1038/nindia.2018.100
  10. Padma TV. It’s time India has a conversation about ethics of gene editing. Hindustan Times. 2017 Dec 18[cited 2019 Apr 2]. Available from: https://www.hindustantimes.com/opinion/it-s-time-india-has-a-conversation-about-ethics-of-gene-editing/story-ihB3o3DbZEvLeXVGdcYZYN.html
  11. Mahajan V. White coated corruption. Indian J Med Ethics. 2010 Jan-Mar; 7(1):18-20. Available from: https://ijme.in/articles/white-coated-corruption/?galley=html
  12. Ahuja SK. Not first time for Dr Amit. Hindustantimes.com. 2008 Feb 5 [cited 2019 Mar31]. Available from: https://www.hindustantimes.com/india/not-first-time-for-dr-amit/story-ya0pe7IX1hq0g9nIY3riSI.html
  13. Ahuja A. Fair chance: How Indian voters use skin colour to choose candidates. Huffington Post India. 2017 Jul 28[cited 2019 mar 30]. Available from: https://www.huffingtonpost.in/amit-ahuja/fair-chance-how-indian-voters-use-skin-color-to-choose-candidat_a_23053514/
  14. Rodrigues C. India’s unfair obsession with fair skin, its impact on relationships. Hindustantimes.com. 2015 Mar.20[cited 2019 Mar 31]. Available from: https://www.hindustantimes.com/sex-and-relationships/india-s-unfair-obsession-with-fair-skin-its-impact-on-relationships/story-cbkOW7ZShgbR10i5yfvIXI.html
  15. Dasgupta P. Discrimination based on skin color at the workplace. SHEROES. 2016 Dec 29 [cited 2019 Feb 1]. Available from:https://sheroes.com/articles
  16. Mackenzie D. Technology driving rise in abortions of girls in India. New Scientist. 2015 Feb 4 [cited 2019 Mar 31]. Available from:https://www.newscientist.com/article/mg22530074-400-technology-driving-rise-in-abortions-of-girls-in-india/
  17. Seven brothers. Economist. 2011 Apr 9 [cited 2019 Mar 31]. Available from:https://www.economist.com/asia/2011/04/07/seven-brothers
  18. Tripathi A. Sex determination in India: Doctors tell their side of the story.” Scroll.in, 2016 Apr 13[cited 2019 Mar 30]. Available from: https://scroll.in/article/805064/sex-determination-in-india-doctors-tell-their-side-of-the-story
  19. Iwamoto K. Asia’s gender imbalance Is bad news for growth. Nikkei Asian Review. 2017 Apr 13 [cited 2019 Mar 32]. Available from: https://asia.nikkei.com/Economy/Asia-s-gender-imbalance-is-bad-news-for-growth
  20. Katyal R. India census exposes extent of poverty. CNN.com. 2015 Aug 3 [cited 2019 Mar 30]. Available from: https://edition.cnn.com/2015/08/02/asia/india-poor-census-secc/index.html
  21. Dubey R. Income inequality gets worse; India’s top 1% bag 73% of the country’s wealth, says Oxfam. Businesstoday.in 2019 Jan 30[cited 2019 Mar 31].Available from: https://www.businesstoday.in/current/economy-politics/oxfam-india-wealth-report-income-inequality-richests-poor/story/268541.html
  22. Balarajan, Y, Selvaraj S, Subramanian SV. Health care and equity in India.. Lancet 2011 Feb 5;377(9764):505–15. Available from:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093249/
  23. Govt mass media campaign highlights the link between tobacco and TB.ETHealthworld.com 2015 Mar15[cited 2019 Mar 30]. Available from: health.economictimes.indiatimes.com/news/policy/govt-mass-media-campaign-highlights-the-link-between-tobacco-and-tb/63316056.
  24. Lyn TE. New malaria estimate says 205,000 die in India.Reuters.com., 2010 Oct 20 cited 2019 Mar 30]. Available from: https://www.reuters.com/article/us-malaria-india/new-malaria-estimate-says-205000-die-in-india-idUSTRE69J6BX20101020?pageNumber=1
  25. PTI. 42 per cent global child deaths due to diarrhoea in India, Nigeria.e Economic Time.in, 2017June 2 [cited 2019 Mar 31]. Available from: https://economictimes.indiatimes.com/industry/healthcare/biotech/healthcare/42-per-cent-global-child-deaths-due-to-diarrhoea-in-india-nigeria/articleshow/58966874.cms
About the Authors

Farhad Udwadia ([email protected])

University of British Columbia Faculty of Medicine, Vancouver, British Columbia, CANADA; Neuroethics Canada Office, Koerner Pavilion, 2211 Wesbrook Mall Room S124, Vancouver, BC V6T 2B5, CANADA

Shivam Singh ([email protected])

Independent Researcher, University Health Network (UHN), Toronto, CANADA

Manuscript Editor: Vijayaprasad Gopichandran

Peer Reviewers: Two anonymous reviewers,

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