By Vijay Chandru
A peep into the human genomic makeup is no more the preserve of the well-heeled. Today, thanks to technological advances in India and across the low and middle income countries, there is a democratization of genomics happening with widening access. It is therefore really about genomics becoming accessible for public health and a market at population scale which gives India a fantastic advantage of scale with its strengths in telecommunications and fintech. India has been aggressive
in building the necessary infrastructure and human capital to be a front runner. The pandemic was a trigger for India to invest heavily in capacity for diagnostics and genome sequencing.
The genetic diversity of India is just beginning to be understood. Today, you can get a whole exome sequence analyzed at a depth of 120X with genetic counselling by a CAP (College of American Pathologists)-accredited lab for under Rs.15,000 which is perhaps already the world’s most affordable genomic health insights test. The target would be to get it to a
third of this cost to see population scale effects of the democratization of genomics. Genomic Health Insights: Solving diagnostic odysseys of patients with genetic disorders has been a challenge the world over. Unfortunately, these options are still only open to a small fraction of those who need it. If there is an alignment of incentives for early resolution and precision diagnosis, it can lead to enormous savings of disability-adjusted life years of tens of millions of affected and their caregivers.
Despite these challenges in public health systems, the empirical evidence of geneticists and treating physicians is starting to gain traction. Here are some early insights from an evolving study of a representative sample of healthy Indians:
- Over 70% in it seem to have useful pharmacogenomic insights on important medications.
- Also, 40% of those sequenced have insights on health risks that they can act on. These include risks from carrier mutations that could affect progeny, hereditary cancer, cardiovascular genetic factors and genetic factors in metabolic disorders.
- Over a third of the population studied have a genetic recessive carrier risk. The ones we see most often are beta-thalassemia, ataxia telangiectasia, cystic fibrosis and spinal muscular atrophy (SMA).
- Only a small fraction of cancer cases occurs because of hereditary risk but when they do, the cancer can be more aggressive and occurs at an earlier age. Any family history of cancer needs to be noted in a risk calculator by trained genetic counsellors for advising family members. BRCA mutations causing breast and ovarian cancers in women an colorectal cancer in men are often discussed but actually close to 100 genes are associated with well-known hereditary cancer risks.
The world’s most populous nation is facing serious health risks due to its genomic traits and social practices of endogamy. This has become clear to the health authorities and discussion of rare and orphan disease challenges are now often in public media with human interest stories of specific cases.
The national policy for rare diseases (NPRD) instituted by the Government of India in 2021 helped to build the first national registry of orphan diseases at the ICMR (Indian Council of Medical Research) and various research programs were initiated at the DBT and ICMR to support centres of excellence (COE) for orphan and rare genetic diseases. NIDAN (National Inherited Disorders Administration) Kendras for diagnostics and focussed effort on aspirational districts for preventive
action.
These are important first steps towards developing genome-based precision medicine in India and taking forward the mission of no disease orphan by 2030.
Registry: Evaluating Disease Burden and Digital Public Infrastructure: A rough estimate is that somewhere between 50 – 100 million Indians are affected by orphaned and rare genetic disorders. Orphaned because either public health agencies deem them rare and therefore low in priority for a nation beset by many health crises, or orphaned simply because commercial pharmaceutical industry and private healthcare providers do not see a market fit for products and services within
their capacity to provide. The payer sector (insurance both public and private) would be responsive once the pharma and providers are active and the actuarial calculations suggest that genuine value can be delivered.
The DBT (Department of BioTechnology, Government of India) has undertaken a bold experiment to build the Genome India database of 10,000 whole genomes as public digital infrastructure. The goals and impact of Genome India are to create an exhaustive catalogue of genetic variations in Indians and a reference haplotype for Indians by carrying out whole genome sequencing of 10000 samples from 100+ communities. Design genome-wide and disease-specific genetic panels
for low-cost diagnostics and research. The speed at which sequencing based technologies are becoming affordable and a forward-looking policy would help focus on sequencing panels to drive screening and diagnosis. The Genome India project wants to develop a biobank of 20000 blood samples to localize genomics research.
A genuine obstacle for the registry is the issue of privacy of health data and the enormous risks of discrimination that an identified affected individual and their family and community faces. This can be a huge disincentive for compliance.
Social Awareness & Prevention: In addition to the core national registry of rare disease patients, we will need a social awareness campaign at the scale that we have seen the tobacco eradication campaigns now active across the country having impact. The causal link to lung as well as head and neck cancers have made the campaign effective. We could of course make similar communication content that links risk of serious genetic disorders with continued practices of
endogamy and consanguinity. However, since this social behaviour is deeply rooted in cultural and community norms, a more effective strategy would be to encourage counselling, screening and consideration of IVF and prenatal testing in high-risk situations. Since every 25th Indian seems to be a carrier of Beta-Thalassemia – we could expect around 10,000 babies a year born a Thalassemia major.
India is now intending to screen every pregnant woman for carrier status in major initiatives at Government hospitals. The burden of disease has now triggered action and screening and prevention of sickle cell and thalassemia are now a priority
in several states. There could be social consequences of carrier status becoming public and will need careful handling of privacy and counselling of families. FOGSI (Federation of Obstetric and Gynaecological Societies of India) has a large responsibility to see this through. The other hemoglobinopathy of epidemic proportions is Sickle Cell Disease which has strong prevalence in tribal populations of India. The Ministry of Tribal Welfare anchors the National Sickle Cell Anaemia
Elimination Mission in coordination with the National health Mission.
Some effective social communication is required for better compliance and voluntary participation. Effective digital intervention could play an important role in creating scientific awareness and gradually chip away at the social stigmas of genetic traits and awareness that early detection and preventive healthcare interventions can manage many of these genomic quirks that we carry. Digital (mobile) games introducing genetics and the genetic health insights are effective ways of educating young people and making them aware of some of the risks associated with carrier genetic biomarkers that so many of us are affected by. Storyboards turned into vignettes and graphic novels and voice and video delivered content using AI to localize and deliver in local dialects should be very possible with the tremendous progress being made through the Bhaasha and Vaani initiatives.
These will gradually chip away at the stigmas that our society still carries. The exciting developments in orphan disease therapeutics are great opportunities for the new deep science innovation capacity in India to make inroads with. The traditional protein replacement therapies and particularly the very new cell and gene therapies will make Amrit Kaal a reality even for these children of a lesser God.
About Author: Vijay Chandru leads the No Disease Orphan 2030 Mission at the Centre for Health, Education and Technology at IIACD in Bangalore. Professor Chandru co-founded Strand Life Sciences and CrisprBits and serves on the faculty of the Centre for Brain Research at Indian Institute of Science which anchors the Genome India project.
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