When five-year-old Suraj was debilitated with a persistent fever, his family took him to the district hospital in Nuapada in western Odisha. The hospital directed them to the Veer Surendra Sai Institute of Medical Sciences and Research at Burla in Sambalpur, around 250 km from their village. At the Institute, Suraj underwent a diagnostic test called haemoglobin electrophoresis to detect whether he had sickle cell disease (SCD). When the tests confirmed SCD, the Institute registered him as a patient and referred him to Nuapada district hospital for blood transfusions.
Suraj’s story came up during our work with the National Human Rights Commission in 2019. It provides a glimpse of the difficulties that people like Suraj, from marginalised tribal communities, face even to access basic healthcare and diagnostics.
It is, however, the beginning of an arduous battle with an under-resourced health system, inadequate information, and high expenditure.
In light of these realities, and the global discussion on advances in human genome editing, the question that becomes especially pertinent is whether these conversations allow for and are cognisant of such experiences.
SCD is an inherited haemoglobin disorder in which red blood cells (RBCs) become crescent- or sickle-shaped due to a genetic mutation. These RBCs are rigid and impair circulation, often leading to anaemia, organ damage, severe and episodic pain, and premature death. India has the third highest number of SCD births, after Nigeria and the Democratic Republic of the Congo. Regional studies suggest approximately 15,000-25,000 babies with SCD are born in India every year, mostly in tribal communities.
Per the 2023 ‘Guidelines for National Programme for Prevention and Management of Sickle Cell Disease’, of the 1.13 crore persons screened in different states, about 8.75% (9.96 lakh) tested positive. It is also one of the 21 “specified” disabilities listed in the Schedule of the Rights of Persons with Disabilities Act 2016.
Access to treatment as a major issue
In 2023, the Government of India launched the National Sickle Cell Anaemia Elimination Mission, to eliminate SCD by 2047. At present, however, treatment and care for SCD remains grossly inadequate and inaccessible. States with a high prevalence of SCD, particularly among their most marginalised populations, are falling behind in their efforts to reach out and provide basic care to those affected.
An apposite example is the (un)availability of the drug hydroxyurea. It lessens the severity of pain, reduces hospitalisations, and improves survival rates by increasing the size and flexibility of RBCs and lowering their likelihood of becoming sickle-shaped. Yet States are largely unable to provide hydroxyurea for SCD patients, pointing to their inability to purchase, stock, and distribute this drug. Even though the National Health Mission’s Essential Medicines List requires the drug to be availed at the primary healthcare level, hydroxyurea is currently only available in certain tertiary-level facilities, such as medical colleges.
Blood transfusion is another important therapy for SCD, but its availability is limited to district-level facilities. Most block-level community health centres don’t offer them. Even during an emergency, families of SCD patients have to arrange for blood replacement units and pay for expensive private transport. Pain medications, from painkillers to non-steroidal anti-inflammatories and opioids, are also scarce.
Bone marrow transplantation (BMT), until recently the other cure for SCD, is out of reach for most SCD patients due to the difficulty in finding matched donors, the high cost of the treatment at private facilities, and long waiting times in public hospitals. There have been efforts in some states to improve public health facilities but it remains to be seen how successful they are at making care universally available.
Access to and equity of CRISPR
In light of this, the application of the gene-editing technology called CRISPR (short for ‘Clustered Regularly Interspaced Short Palindromic Repeats’) to treat SCD is important – for its novelty and promise but also for the health disparities it makes apparent.
The U.S. Food and Drug Administration recently approved two gene therapies, Casgevy and Lyfgenia, to treat SCD in people ages 12 and older. Casgevy, developed by Vertex Pharmaceuticals and CRISPR Therapeutics and also approved in the U.K., is the first CRISPR-based therapy to have received regulatory approval in the U.S. Lyfgenia, manufactured by Bluebird Bio, doesn’t use CRISPR but depends on a viral vector to change blood stem-cells.
Both treatments entail collecting a patient’s blood stem-cells, modifying them, and administering high-dose chemotherapy to destroy the damaged cells in the bone marrow. The modified cells are then infused into the patient through a hematopoietic stem cell transplant. The treatments are expected to take up to a year and require several hospital visits. Victoria Gray, a patient in her mid-30s from the U.S., was the first recipient of Casgevy in clinical trials. Having been free of SCD symptoms and pain for a few years, she is now seen as a symbol of hope for new therapies.
CRISPR’s inventors have won a Nobel Prize and it is celebrated as a revolutionary innovation, but its treatment cost of $2–3 million keeps it out of reach of most of those affected in countries where SCD is endemic. While researchers and policymakers are considering potential alternatives to improve access in low- and middle-income countries, such high-tech therapies require advanced care in well-resourced hospitals, too, bringing with it challenges of availability, affordability, and quality – which disproportionately affect the poor and marginalised. It raises pressing questions about equity, access, and justice in the use of gene therapies.
CRISPR in India
In India, CRISPR’s possible medical applications also pose ethical and legal quandaries. The National Guidelines for Stem Cell Research 2017 prohibit the commercialisation of stem cell therapies and allow the use of stem cells only for clinical trials, except for BMT for SCD. Gene-editing stem cells is allowed only for in-vitro studies. The Guidelines also encourage (but don’t mandate) the sharing of financial benefits resulting from the commercialisation of stem cell products with the donor or community.
Further, the National Guidelines for Gene Therapy Product Development and Clinical Trials 2019 provide guidelines for the development and clinical trials of gene therapies for inherited genetic disorders. India has approved a five-year project to develop CRISPR for sickle cell anaemia. Under its Sickle Cell Anaemia Mission, the Council of Scientific and Industrial Research is developing gene-editing therapies for SCD. Around Rs 34 crore has been allocated for this mission over 2020-2023. It is reportedly in the pre-clinical stage, with clinical trials awaited.
However, the Guidelines need a stronger health inequity and discrimination perspective, addressing issues such as equitable opportunities for underserved populations to safely participate in clinical trials, and whether and how this therapy will be made available to those populations in future.
Adopting and promoting advanced therapies like CRISPR in India require a comprehensive approach that accounts for inequities and disparities in the country’s overall healthcare access framework. While such advances in curative treatments are encouraging, our concerns are primarily focused on the importance of equity and access throughout the lifecycle of research, development, and implementation of gene therapies.
The development of therapeutic technologies occurs at a pace and level that renders it unavailable to the same constituencies most affected by the disease. The wait for the products of gene-editing to trickle down to the margins is long and often in vain. We suggest investment in expensive therapeutic technologies need to be preceded by focused efforts to first make basic treatment available – such as an uninterrupted supply of hydroxyurea – to those direly in need of treatment.
Deliberations on regulatory frameworks also need to be expanded from closed scientific circles to the larger public. Policies on the development of such technologies need to receive inputs from civil society and patients’ advocacy groups to be able to develop frameworks for ethically responsible research. The need of the hour is an approach that focuses on integrating these multiple issues of access to diagnostics, drugs, health information and community support. It is only then that children like Suraj will be able to live a healthy life in the long term.
Sarojini Nadimpally, Gargi Mishra, and Keertana K. Tella work on public health, bio and reproductive technologies, human rights and gender.
