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‘There is a genomic solution to many of our problems...’

Rakesh Kumar Mishra, director of the Tata Institute for Genetics and Society (TIGS), believes in the power of science and technology to solve pressing societal problems. He also believes that the key here is the ability to take these solutions from the laboratory to the world in the quickest possible time.

A specialist in genomics, the 62-year-old Mr Mishra has a doctorate in chemistry from the University of Allahabad. He has been associated with the Indian Institute of Science, Bengaluru; the University of Bordeaux, France; and the University of Geneva, Switzerland, while also serving as director of the Centre for Cellular and Molecular Biology, Hyderabad. Mr Mishra speaks to Labonita Ghosh about TIGS and the work it undertakes. Excerpts from the interview:

What is the vision and mission of TIGS?

As a nonprofit funded by the Tata Trusts, our purpose is to employ cutting-edge science to find solutions to societal problems. We identify the problem, assess it with high-end science and see if it can be solved. We are involved in a large number of collaborations and institutional partnerships, the aim being to reach our solutions to relevant stakeholders.

We are a programmes-driven institution. What we are not is an individual investigator-driven place where a scientist can keep working on problems lifelong. We change our approach and experimental strategies to stay in step with the changing science and technology landscape.

We have three primary areas of work: infectious disease, crop improvement and rare genetic disorders. Technology has evolved quickly in these three fields over recent years and revolutionised research. Current genetic and genomics technologies enable us to do things differently and more efficiently than 15 years ago.

The technology is ready and the problems are aplenty. We want to connect the two using our resources and collaborations. There is a genomic solution to many of our problems in the areas of agriculture and healthcare.

These are three fields that are very different…

They may appear different but it boils down to our ability to extract genetic material from organisms of interest, read them by sequencing and use or edit them to obtain desirable properties. If you can do all of this, you can apply the same methods to both plants and people, not just to simpler organisms like bacteria.

We are setting up technology platforms where we carry out DNA or nucleic acid-based diagnostics. We can extract DNA and see if we can find a particular ‘signature’ or mutation in the genome that causes a particular disease, be this in plant or animal. It is the same process for infectious diseases, using the same disease-agnostic platform.

What are the costs involved?

We are developing this technology by optimising to our needs and indigenising so that we do it at a very low cost. The point is, can we do it at less than 100 or even 20 per use? Can we do several thousand at one go? Can we employ it in a village which has no electricity or healthcare facilities? These are the challenges in the science and technology part.

Eventually, you need a vehicle to take your solution from the lab to people; industry and entrepreneurs are that vehicle. But they need to see financial viability in the solution, or they will not invest in it. We keep that in mind as our objective is to deliver our solutions to the ultimate stakeholders.

For each activity that we undertake, we try to create a complete platform. Once we have decided on the problem and how to address it, we have to see at what stage we can deliver it to an entrepreneur or company, and what kind of intellectual property protection we can offer so that more companies become interested. We try to seek patent protection for certain things or make it so economical that nobody else can compete. We seek advice from entrepreneurs and industry partners on all these things.

Rakesh Kumar Mishra

Can we have an example of this?

Currently, the diagnostic tests prescribed for dengue or tuberculosis are largely antibodies-based. These are expensive and have several limitations. We are developing DNA/RNA-based tests which will be more sensitive, accurate and cheaper. We may also, with one test, be able to detect chikungunya, dengue and various others, and even be able to tell if there is any coinfection.

We want to do this for as little as 200-300. Having a diagnostics development platform that can be disease-agnostic enables us to provide quick, economical and deployable solutions to existing or new pathogens.

Could you tell us more about TIGS’s work in its three verticals?

Current agricultural practices worldwide don’t take into consideration the cost to the environment and the future damage we are causing with intensive farming. Add climate change, and this will become a serious problem in the coming decades. The world is better off with crops that are climate resilient, pest- and disease-resistant and more nutritious. Our approach in crop improvement enables us to address these issues at one go.

Scientist Harvinder Khera checks bacterial culture being grown in an incubator (this is used to make antibodies in the lab)

In infectious diseases, we work in three areas: vector control, surveillance and anti-microbial resistance (AMR). For vector control we have set up an insectary where we are developing environmentally-safe methods to study mosquitoes and interfere with their feeding, mating and egg-laying behaviours.

We are also developing biological control methods where one organism (for example, certain kinds of bacteria) can control the population or pathogen-carrying features of vectors. In summary, while we can’t kill all mosquitoes, we can make certain environments safe by neutralising species that cause malaria or dengue.

Our wastewater surveillance project involves collecting samples from sewage treatment plants across Bengaluru, studying them for pathogens using DNA/RNA-based methods to identify pathogens and even changes in the pathogen load. We have developed mathematical methods using this data to estimate, for instance, the SARS-CoV-2 viral load of a ward or neighbourhood. In Hyderabad, we’re doing surveillance of wastewater from open drains, which is more challenging.

We want to develop standard operating procedures using these two approaches so that they can be expanded and implemented across the country. Our processes enable environmental surveillance in real time and allow us to know the almost-exact pathogen nature and load of a neighbourhood without touching a single resident.

This is a great thing from the public health point of view and is going to be a key component of the ‘one health’ concept, which is about the realisation that public health must be seen in the context of animal, plant and the entire environment’s health.

AMR is a big headache in major cities and considered a silent pandemic. If we keep misusing antibiotics like we are doing now — for poultry, cattle, fisheries and, of course, through people who buy them over the counter — we are giving pathogens a chance to develop resistance.

When medical staff are faced with AMR cases, they often don’t know what kind of resistance it is or which antibiotic will work. They conduct multiple tests and it takes a few days to figure out the right medicine. At TIGS we want to develop something that can tell the clinician in just two hours what kind of resistance it is and what medication will not be effective.

Part of our work is societal outreach: to educate people and clinicians about the overuse of antibiotics. We also aim to understand the scale and seriousness of this challenge, along with policymakers, government officials and public interest groups.

Your work in the rare genetic disorders (RGDs) space is also quite significant.

This is a programme we started more recently. It is estimated that about 90 million people suffer from RGDs in India, which means this is not quite so ‘rare’. Not much is known about many of these disorders, so we are now developing a database which will have complete, validated information that clinicians can access.

Our existing medical facilities are not enough to care for even a fraction of patients with RGDs — which are usually found in small or marginalised communities — and treatment is prohibitively expensive. Medication has to be imported from abroad because Indian pharma companies do not invest in such a market because it is not lucrative. In most cases, patients die from incorrect diagnosis, rapid progression of the disorder or lack of medication. Quick and accurate diagnosis and access to available interventions can improve survival rates as well as the quality of life of patients.

As RGDs are most often due to consanguineous marriages, one of the ways to create social awareness is to carry a strong, science-based message to people. Once you understand the science, you can go to policymakers and seek the requisite regulations and permissions.

At TIGS we have goals for each activity. Who is the final target? Society. What is the vehicle that will take the solution to society? Industry or a startup partner. All these things have to be brought onto one page. We look at not just solving the problem, but taking solutions all the way to people. There is no point otherwise.