Can Genome Editing Therapies Offer Hope Rather Than Frustration? A Perspective on Ethics in India

Introduction

There is enormous excitement about gene editing opening up a cornucopia of possibilities, curing diseases, fighting infections, and also perhaps boosting intelligence, looks, or extending the human lifespan. In a vast and densely populated country such as India, with a full spectrum of disease variations, there is an enormous potential for targeted treatments involving gene editing. Like many other countries, India is marching ahead on a journey to support breakthroughs in research and keenly looking at this technology to bring transformative solutions to the country’s enormous health problems.

Gene editing studies have the potential to provide access at an affordable cost to the communities and countries where the trials are conducted. Good quality research is needed to address the unmet health needs of people living in resource-limited settings. ¹ Accordingly, for gene editing to be available and useful to the population in India, clinical trials need to be conducted in India. Unless the studies are conducted in low-resource settings, the results and outcomes will not generate generalizable value or be able to reduce the health disparities between lower-income and higher-income countries.

In early 2023, the Indian government announced a national mission to eliminate sickle cell disease (SCD) by 2047. India has among the highest hemoglobin S allele frequencies worldwide, and there is enormous hope that this objective can be achieved.^2,3 For individuals born with conditions such as SCD or cystic fibrosis, the gene variant could be edited out in principle and replaced. Taking this further, imagine curing a disease even before a baby is born. The approval of Casgevy in the United Kingdom in December 2023—the first CRISPR gene editing therapy—marked the start of a new era for gene editing as a therapeutic tool. ⁴ Cures for any incurable disease can be appreciated by any family with a member who is suffering, since diseases put a significant, often lifelong burden on individuals, families, and health care systems.

Lowering costs and increasing access are important goals in India. Chimeric antigen receptor (CAR)-T cell therapy studies in India have shown recent success, despite the complexity of the manufacturing platform, providing solutions for hematological malignancies. India has launched its first home-grown CAR-T cell therapy for cancer, considered a breakthrough in the fight against cancer and more affordable than similar therapies in developed nations. The results from the first-in-human clinical trials will help to improve understanding of the cost implications from development to delivery and show promise in terms of affordability. ⁵ An affordable platform of cell and gene therapy would be poised to create transformational change as a mass therapy to a broader socio-economic range of patients. However, the knowledge and necessary skill sets remain limited to a few tertiary care centers, as scale-up requires extensive investments in education, training, and core infrastructure.

The recently initiated Genome India Project aims to bridge the infrastructure gap by facilitating the development of effective treatments for such conditions across the country. This landmark initiative involves mapping India’s diverse genetic landscape toward advancing precision medicine, empowering health care in India to deliver tailored, effective, and equitable treatments addressing specific genetic variants, and providing insights into the health patterns of India’s many communities (Fig. 1). ⁶

OPEN IN VIEWER

FIG. 1.

Genome India Initiative involving 20 institutions across India. ⁶

In addition to considering their medical promise, it is critically important to discuss how these technologies may impact our lives. What ethical values and norms should guide these developments in science? How should countries in low- and middle-income settings be represented at the global level where decisions are being made? These stakeholders must be able to voice their concerns, needs, and requirements so that the technology is not limited to serving a few in the developed world but rather is made relevant, available, accessible, and affordable to people across the globe.

Moral and Ethical Dimensions of Gene Editing

UNESCO’s Universal Declaration on the Human Genome and Human Rights regards the human genome as the “heritage of humanity” to be protected and passed onto future generations. ⁷ Scientific advances must be considered in light of human rights. Gene editing has huge potential to revolutionize medical treatment, offering the possibility of targeted interventions or therapies for some untreatable diseases. Scientists in India and around the world are trying to develop the roadmap to cure genetic disorders such as SCD and Duchenne muscular dystrophy. Despite its enormous potential, there are difficult questions around long-term safety, unwanted and unintended consequences of gene modifications, and dilemmas about how far one can go. Somatic cell gene editing allows non-heritable changes to treat many genetic diseases and some cancers and is far less controversial, as the changes are not transmitted to future generations.

By contrast, human heritable genome editing (HHGE) has major implications for potential misuse, concerns about eugenics, and long-term effects. Should gene editing to address diseases be treated like any other therapy, or do we need stricter controls through a regulatory and legal framework with provisions to protect people from harms specific to this technology? Should gene editing become a mainstream mode of treatment, and if so, what would be the moral boundaries of permissibility? Can the technology trigger freak changes that might disrupt the environment, leading to irreversible damage to biodiversity? Similarly, gene editing of human embryos raises difficult ethical questions regarding non-therapeutic modifications, including selecting for preferred physical or cognitive traits. Should parents have autonomy to have their children’s genes edited for selective traits such as good looks, height, or intelligence, leading to the creation of “designer babies”? Further, commercialization and patenting require due consideration. Other emerging questions and concerns will emerge with time.

India’s diversity in terms of socio-cultural landscape, environmental geographies, ethnicity, economic status, literacy, and health profiles adds to the complexity of undertaking gene editing research. Ethics must be the guiding light: ensuring voluntary participation, informed consent and a good understanding of risks and benefits among diverse population groups needs careful navigation with sensitivity, and respect for local cultural norms, values, and belief systems. There are concerns that gene editing could exacerbate existing social divides, generating further stigmatization or discrimination against persons or groups based on their genetic makeup. Some Indian researchers are accordingly focusing attention on diseases that predominantly affect the disadvantaged, tribal populations of the country suffering from SCD as well as varied hemoglobinopathies. ⁸

Scientifically speaking, the most significant risk in the context of human gene editing is its potential for unknown and unintended consequences. Editing one gene may lead to off-target mutations, which may have health implications with unpredictable consequences for the present generation or generations to come. On the one hand, we have real promises for a cure; on the other, we are not certain about both the short term as well as long-term outcomes. When research involves young children with high-risk procedures and long-term implications, it may not be easy to provide all the explanations to parents and the high risk involved, making the process even more challenging. Adequate efforts are required toward improving understanding and communications as well as building capacity, networks, fostering collaborations, and building public trust as we connect science with society. ⁹

In addition, there are overarching concerns that if the technology is not carefully managed, it could become a tool accessible predominantly to the wealthy, widening the socio-economic divide. Ensuring the privacy and security of personal genomic data is another major concern requiring clear-cut measures to safeguard this information. ¹⁰

Governance Framework in India

A governance and regulatory framework around gene editing will be able to guide the technology’s potential for profound and potentially irreversible impacts on future generations, necessitating careful consideration of safety, ethics, and societal implications. The existing governance framework in India provides a multi-tiered regulatory and ethical oversight system involving several agencies.

In 2017, the Indian Council of Medical Research established the National Ethical Guidelines for Biomedical and Health Research Involving Human Participants. With a chapter focused mainly on human genetics research, including gene editing, the guidelines set the stage to encourage research on gene editing by providing a broad ethical framework. ¹¹

The regulatory framework for clinical trials in India is governed under the New Drugs and Clinical Trials Rules (2019). These rules have categorized Gene Therapy Products, including those developed through gene editing, as new drugs that require approval through the Central Drugs Standard Control Organization (CDSCO), the Drug Regulatory Agency in India under the Ministry of Health and Family Welfare. ¹² Both somatic and HHGE hold the promise; however, due to the ethical and moral implications, the regulatory pathways are distinct. Germline, in utero gene therapy, or xenogeneic therapy involving different species is prohibited in India; however, in vitro research studies involving genome modifications to an embryo up to 14 days of fertilization are allowed. There is a well-defined review, approval, and monitoring framework. The “Institutional Bio-Safety Committees” review and monitor any genetic manipulation, ensuring compliance with biosafety rules and submit recommendations for further approvals to the “Review Committee on Genetic Manipulation” set up by the Department of Biotechnology. ¹³

In India, genetically modified organisms and their products are regulated by the Environment (Protection) Act (1986) and the “Rules for the manufacture, use, import, export, and storage of hazardous microorganisms, genetically engineered organisms, or cells (1989).” ¹⁴ Furthermore, the Genetic Engineering Approval Committee approval may also be required if there is any release of a recombinant product into natural environments, to assess their long-term interaction with the environment or if that poses risks to ecosystems or public health. ¹⁵ In addition, there are specific provisions related to the export or import of genetically modified products, which require permission from the “Directorate General of Foreign Trade”. ¹⁶

Ethics Review of Gene Editing Research

Addressing the variety of ethical challenges is crucial for promoting clinical research that protects the rights and well-being of individuals. An independent and thorough ethics review may help to ensure the rights and safety of participants. To be competent and facilitating, the ethics committee members would need appropriate prior training to have a clear understanding of their role and responsibilities. Ethics committees may recruit members or invite independent consultants with special expertise to improve understanding and thereby aid in the decision-making process. The ethics review should be followed by close monitoring and oversight of research to ensure that protections are in place. ¹¹ Several aspects may be reviewed by an ethics committee (see Table 1).

Accessibility and Affordability

To date, innovative gene editing-based treatments that carry high development costs are exorbitantly priced and inaccessible to the public. As genomic technologies advance, there is a risk that these innovations will primarily benefit wealthier people, widening existing divides. Rather than offering hope, these therapies may offer “frustration” as the treatment, although available somewhere, may be out of reach. Few, if any, insurance companies or agencies would be in a position to cover the projected treatment costs of around $2 million per patient, limiting their accessibility in lower resource settings such as India. ¹⁷

It is critically important to consider developing local solutions at an affordable cost, as evidenced by the Covid-19 vaccine Covaxin, which was developed indigenously and affordably in a limited timeframe—India has the potential to make similar moves with genomic technology. Encouraging meaningful public–private partnership can help in reducing production costs and improving scalability at the local level would bring down the cost of treatment. Initiatives that involve technology transfer, and cost-sharing could also improve accessibility. Concerted local efforts are needed to undertake cutting-edge research, ensuring regulatory compliance, finding ways to improve public–private partnership, ensuring good manufacturing practice standards and quality before producing treatments at scale. However, the inadequate infrastructure remains a significant challenge, and support from the government is needed to build facilities and plan policies to develop therapies. Given the huge burden of disease in India actually making this innovative therapy accessible and affordable is a daunting task. ¹⁸

Public Understanding and Engagement

As gene therapy becomes more widely available, there will be a need to educate people about the benefits and risks. In parallel, there is a need to encourage more students to pursue careers in genetics, artificial intelligence, and biotechnology and provide them with suitable research and training fellowships. It is further important to teach scientists and policymakers about the technology and its ethical implications. An open and transparent dialogue would need to bring all stakeholders on board, including the general public. ¹⁹

An informed society is better equipped to make responsible decisions about its future. Capacity building and collaborations are the key. Currently, only a few Indian institutions have the necessary infrastructure to undertake intensive research in gene editing. These opportunities must be extended to others to create a broader pool of trained professionals. India’s diverse socio-economic, religious, and cultural landscape presents unique ethical, legal, social issues. Responsible innovation is required, as the technology presents challenges that can widen existing inequalities or may conflict with traditional beliefs and values and its limited access may exacerbate equity.

The present regulatory oversight may be limited to ensure against possible misuse or discrimination, and public engagement and education may help reduce fear or misinformation. For equitable access and affordability, this work needs to be well integrated in the national programs to deliver quality outcomes for all. A dialogue between technologists, policymakers, and communities can help gene editing initiatives better align with human values. Collaborative efforts should be characterized by clear objectives, shared responsibilities and considerations for data sharing, publications and patents, while ensuring respect for individual privacy in the sharing of biological material and data.

Engagement with patient advocacy groups and non-governmental organizations working for their cause will be very useful. Communicating gene editing research to the public requires clarity, transparency, and careful consideration of ethical and social implications. Encouraging public dialogue and including diverse voices in the conversation helps ensure that societal values are taken into account. The media has a critical role to play in providing information and dispelling the fear that is spread through misinformation. Scientists have a responsibility to inform the public in a simplified manner and to present evidence-based facts and clarify misconceptions through public platforms, social media, and trusted news outlets. Patient advocacy groups in India have been working and raising awareness toward funding and legislative support and have supported setting up disease registries as well as the creation of a Rare Disease Policy. ²⁰ Educational institutions should foster an environment conducive to cutting-edge research and innovation, provide independence for scientific exploration, and offer the necessary infrastructure. In parallel, a significant effort is needed to initiate dialogue, foster collaboration, and build trust among all stakeholders.

Evolving Role of Global South Including India

Countries in the Global South including India have an important responsibility to effectively contribute to the global dialogue to set up equitable frameworks and to not just be a passive bystander. They need to be at the forefront to contribute to the evolving ethical guidelines and standards at the international as well as national level, advocate for affordable access to applications, to share the conditions in the South and plan building capacity at the same time. All this is important to meaningfully contribute to collaborative efforts while emphasizing on local perspective, building in safeguards against potential discrimination or misuse, so that benefits can be equitably available and shared. As International frameworks evolve, the strong voices from the South and discussions around scientific and ethical aspects can help to balance innovative advancements with the requirement to ensure the safety and well-being of the people.

Conclusion

Gene editing has huge promise; however, we must ensure a strong framework for governance for its applications to be morally and ethically relevant. There is a need to make gene editing and other advanced medical technologies available not just to the privileged but to the common person, so as not to further widen the gap between those who can and cannot afford them. The challenge lies in dispelling unwarranted fears and ensuring gene editing is used for the betterment of many. To ensure equitable access, it is imperative to adopt a comprehensive strategy that encompasses affordability, ethical practices, support, and steps to build infrastructure and capacity. Further, to ensure the safe and ethical use of this technology, there is a need to collaborate and create networks of scientists, ethicists, policymakers, as well as public representatives to oversee its applications. In India, significant support from government agencies and public–private partnership will be critical to reaping the fruits of genetic technologies. Concerted efforts to educate, train, and develop the necessary skill sets, along with advocacy, and building public trust will help to improve acceptability. Issues around equitable access and affordability particularly necessitate wider discussion.

Gene editing is not just another innovation. It has the potential to improve all human life. The ethical, moral, and legal aspects of these technologies need to be fully integrated as we prepare to accept the implications they may have for our lives.