Medical moonshots

After over a decade of pursuing a research career abroad, Sarvesh Kumar Srivastava returned to India in 2023. He joined the Centre for Biomedical Engineering at the Indian Institute of Technology (IIT) Delhi, where he started an interdisciplinary research group. Coincidentally, that year India landed a rover on the Moon's South Pole, a global first. Inspired by the successful Chandrayaan-3 mission, the country's apex agency for biomedical research, the Indian Council of Medical Research (ICMR), decided to fund moonshots in healthcare.

Srivastava is among the beneficiaries of a pioneering ICMR award in 2025, which seeks to support disruptive and original concepts that have yet to qualify for conventional funding. He develops microscale devices that allow insulin to be taken orally by enhancing its absorption in the gut. An oral insulin could prove revolutionary for millions of people with diabetes, who have no choice but to inject insulin daily to control blood glucose (see 'Small is big'). To bring real change, researchers must push boundaries, says Srivastava. But such an approach demands intrepid backers. "You need someone who says: 'You go try. If you fail, no problem'," he says. "(The award) will help researchers push boundaries."

Launched in 2024, the 'First in the World (FIW) Challenge' research grant seeks to fund high-risk, high-reward healthcare innovations that could lead to products, technologies or solutions that are truly first in the world. The challenge is open to all: researchers at private companies are among those who have qualified. The review process is institution-agnostic — to ensure a level playing field and encourage innovation from all sectors, says Taruna Gupta, Scientist G & Head, Development Division at ICMR.

The funded ideas span a spectrum, including diagnostics and therapeutics. They aim to tackle intractable healthcare challenges such as diabetes, drug-resistant infection, and cancer.

The grant differs from traditional funding mechanisms in several ways, Gupta says. "It encourages bold, unconventional thinking rather than incremental research," she explains. "Proposals are evaluated on novelty, global first-mover potential, and anticipated impact." This focus on unsolved problems is a different lens from the usual, urging Indian scientists to lead rather than to follow, says Utkarsh Palnitkar, an independent life sciences consultant who has advised and been closely associated with Central and State government initiatives to boost healthcare innovation in academia and industry. "It will provide an impetus to look at novel research, which has always been a challenge in the country."

At the University of Delhi South Campus, it led Amita Gupta and her team, for instance, to think out of the box and beyond routine research. The Professor and Head of the Department of Biochemistry won the grant for a rapid test that checks whether donated blood is free of a clutch of pernicious infections (see 'Green signal for red').

The FIW Grant amounts are significantly higher than typical grants, in crores of rupees rather than lakhs (see table: 'Cut above the rest'). The aim is to de-risk early innovation and accelerate translation while pushing the frontiers of medical science. Researchers are funded to develop demonstrable prototypes and to create a readiness for regulatory pathways or commercialisation. This could be a lifeline for start-ups that are too early in the product lifecycle to attract private funding (also see 'Indian start-ups dive into deep tech phase'). "These kinds of grants are very, very helpful, to take the prototype to the product level," says Shailesh Govind Ganpule, Associate Professor at IIT Roorkee.

Palnitkar suggests wider promotion of such an initiative, such as by partnering with trade associations. More important, there should be clarity on how to move forward. "There have to be mechanisms of assistance beyond writing the cheque."

Many proposals articulate original solutions addressing unmet clinical needs, and show clear potential for global leadership, says Gupta of ICMR. 
Shaastra chronicles a few that made the cut.

Boosting immunity to tackle infection.

Since it serves as the basis for proof of concept, the test itself must be foolproof. The ICMR award will be used to validate the test and deploy it to identify molecules that could activate the overexpression of HDPs. Successful in vitro testing will have to be followed by animal studies. If one or more compounds clear these, they will have to be tested in specific infections, such as those of the skin. They may need industry partners for further development. "I am not expecting a cakewalk."

As microbes become increasingly resistant to antibiotics, the world urgently needs a variety of new and potent agents to face them down, as the drug industry's resources are flowing towards more lucrative disease areas such as cancer and obesity.

Creating microdevices for oral insulin absorption.

Srivastava's prototype looks, behaves and performs like a capsule, he says. To maximise absorption, it is designed to release insulin only in the presence of what he calls "activation switches". The acids, enzymes, and microbes of the GI tract are all potential stimuli, he says. The researchers are also fine-tuning an insulin formulation for the microdevice to deliver. Globally, self-organising microdevices are being tested for biomedical applications that require highly precise navigation and control, such as imaging and drug delivery. But they face many hurdles on the way to the clinic.

The prototype will undergo pre-clinical studies on animals. If it clears these, it will undergo human trials.

Nearly 24 crore Indians live with either diabetes or pre-diabetes, Srivastava observes, quoting statistics from a 2023 ICMR study. His goal is to bring a solution that capitalises on India's strengths in oral drug delivery, he says.

Using diagnostic X-rays for therapy.

The intensity of diagnostic X-rays is typically one-thousandth to one-hundredth of that of radiotherapy. A lower dosage is less damaging and is better for imaging, but not strong enough to kill cancer cells. To enable low-dose diagnostic X-rays to kill cancer cells, Rengan wants to use specially designed nanomolecules that can radiosensitise cancer cells — making them absorb more radiation even with low-dose X-rays.

In collaboration with other researchers in chemistry, he is currently developing these nanomaterials "We are now working with gold, ruthenium, silver, and many other materials. These are molecules where they have atoms of inorganic material bound to other groups," he says. Some of the nanomaterials he is developing behave like cisplatin, a platinum-based chemotherapy agent that has been in therapeutic use for a long time. It has good radiosensitising abilities as well. Referring to cisplatin, Rengan says that there are chemotherapy drugs on the market that also act as radiosensitisers. While this is not entirely new, the existing drugs cannot "drastically" reduce the dosage. "Instead of, say, where you use 10 grays, you may reduce it… to maybe 5-6 grays, but it is not going to go to that level of ultra-low dose," he says. With the nanomaterials that Rengan and his colleagues are preparing in the lab, the required dosage can be 1,000 times lower than the current radiotherapy dose." These nanomaterials are working like a chemotherapy agent and also acting as a very good radiosensitiser," he explains.

Currently selected for level 1 of the ICMR FIW grant, Rengan and his colleagues are working to generate preliminary data and then apply for level 2 of the grant.

A rapid four-in-one test seeks to make blood donations safer.

Amita Gupta is an old hand at developing rapid diagnostic tests. Back in 2001, she was part of a team of researchers that developed NEVA HIV, a rapid HIV diagnosis kit that was later acquired by Cadila Pharmaceuticals. Gupta always felt that the basic technology developed for NEVA HIV could be translated into tests for other diseases. "It's like a platform technology that can be adapted for any infection," says Gupta, Professor and Head of the Department of Biochemistry, the University of Delhi South Campus.

When Gupta first found out about the FIW grant, she knew it was time to develop another blood-based test. Not just for HIV this time, but a set of four diseases — HIV, hepatitis C, hepatitis B and syphilis — that every bag of donated blood must be tested for.

The current standard practice is to collect blood at donation camps and transport it to labs for processing. After that, it is tested and discarded if found to be infected with any of the diseases. Only uninfected blood is stored and used for transfusion purposes. Although this is the standard practice nearly everywhere in the world, Gupta identifies several problems with this methodology. In this process, blood is processed by lab workers before being tested for infection. This means that, from the donation site to the lab, there is a chain of processing, and at each step, there is a risk of exposure to contaminated blood. "This is a biohazard," she says.

Gupta feels that blood should be tested before donation, rather than unnecessarily taking blood from a person who is not fit to donate it or is currently carrying an infection. Additionally, it will minimise the disease exposure risk for healthcare workers and lab technicians, and the risk of contamination from blood bank leaks. "We want to develop a test that could be done on site, prior to the collection of blood, so that this entire process and supply chain would be free of risk and hazard," she says.

Since receiving the FIW challenge grant, Gupta and her colleagues have been developing reagents that will enable testing for the four blood-based infections in minutes. For each of the four diseases, separate testing reagents have to be developed and then validated for performance, specificity and sensitivity of detection. After individual reagents demonstrate acceptable performance, the researchers will prepare a cocktail of reagents to enable a single test for all four diseases. Tie-ups for initial testing of reagents for each disease are already in place with blood banks. However, once the reagents are ready and validated at a small scale, larger evaluations will be done, and eventually, industry partnerships will be required to take it forward. ICMR's support in running multicentric trials across the country would be crucial, but that is at least a couple of years away. "We are looking at a two-to-three-year timeline to have the cocktail ready," she says.