What’s on the mind: Inside IIT Madras’s Brain Centre

Folkerth, now a visiting fellow at SGBC, is not the only one impressed with the new centre. The new brain research infrastructure has begun to attract the attention of leading neuroscientists from around the world, with several international collaborations stitched up.

Looking at the brain

It is not that human brains have never been mapped or imaged before. Early efforts were made decades ago. Several institutions in the United States, Japan, Germany and China have been mapping the human brain and have prepared different kinds of brain atlases. Most of these either attempt to capture intricate details of very small sections of the brain or larger features of a whole brain.

SGBC is doing both, capturing high-resolution cell-level details of the entire brain, allowing one to zoom into any section and look at individual cells. And the plan is to do this for hundreds of brains — perhaps the most ambitious attempt ever to create a reference human brain atlas, one that will result in cellular-level brain maps of people across ages, population groups, ethnicities, and disease conditions.

Kris Gopalakrishnan and Professor Mohanasankar Sivaprakasam. (Express photo)

“We have attempted something very ambitious that has never been done before. Now that we have created a full-fledged technology platform, we are rapidly scaling in our mission to generate the most detailed set of human brain maps across human life and analyse them at different levels. We strongly believe this will lead to fundamental breakthroughs in understanding of human brain functioning, intelligence, ageing and neural disorders,” says Professor Mohanasankar Sivaprakasam, head of the Sudha Gopalakrishnan Brain Centre, as he shows us around the recently expanded facility at IIT Madras.

Two years ago, the centre released its first dataset: three-dimensional digital reconstructions of five foetal brains, aged 14-24 weeks of gestation. It’s the most comprehensive cellular-level mapping 1of the human brain in its early stages of development. More datasets are expected to come out this year.

The brain of the matter

For India, the early success of SGBC has a significance that goes far beyond the mere creation of a world-class scientific facility. The centre is an excellent example of the kind of projects that can propel India to the global stage, demonstrating that it is possible to make low-cost, high-impact contributions in areas that are globally relevant and in high demand.

The centre also is highly interdisciplinary — with expertise drawn in from engineering, neurosciences, computing, imaging, data sciences, medicine, and more — the kind of collaboration that’s considered essential in modern-day research. Besides, the project has had a very quick turnaround time – the proposal was made in 2018, the centre became functional in 2022, and the first dataset, along with a detailed paper, was released in 2024.

Most importantly, the centre is a unique case of a philanthropy-led initiative. While the government provided the crucial seed money, the bulk of the funding came from private sources, most of it from the Pratiksha Trust founded by Infosys co-founder Kris Gopalakrishnan and his wife Sudha.

In fact, it all began with Kris’s decision to set up three chair professorships on computational brain research at IIT Madras in late 2014. Gopalakrishnan had stepped down as CEO of Infosys in 2011, and decided to use his substantial personal wealth to promote science and technology in India. Earlier in 2014, he had established the Centre for Brain Research at the Bengaluru-based Indian Institute of Science and wanted to strengthen that effort by setting up these chairs at his alma mater, IIT Madras.

“There were two reasons for my interest in brain research. Improved understanding of brains is what has led to recent breakthroughs in computing — development of neural network architectures, machine learning and artificial intelligence. I was convinced that newer and better models of computing would come up if we understood the brain even better. At the same time, I wanted to support something that was socially relevant. India has a growing number of aged people. More and more people would be affected by age-related disorders such as dementia, Alzheimer’s and Parkinson’s, for which we have no solutions right now,” Gopalakrishnan says in an interview to The Indian Express.

The first to take up chair professorships was Partha Mitra, a theoretical physicist-turned-brain researcher who was working at Cold Spring Harbor Laboratory (CSHL) near New York.  Mitra had been looking at brains through a physicist’s lens, trying to understand the connections and circuitry in brain cells of mice and monkeys.

“The offer at IIT Madras seemed to be a good match to what I was already doing. And I could see the potential to do something more and new. So, you can say, I had my own scientific agenda, and IIT Madras welcomed the ideas and vision,” says Mitra.

The new position required him to make two to three visits to IIT Madras a year, and build a programme around computational neuroscience – using mathematics, computer models, and data analysis to understand how the brain works.

But he nurtured another desire — for someone who had been opening up the brains of mice and monkeys, he wanted to scale up his study to human brains. He says that during his conversations with researchers at IIT Madras and elsewhere, he would often talk of the need for a human brain programme in India but “did not receive much attention”.

Until he got in touch with Mohanasankar Sivaprakasam from IIT Madras’s Department of Electrical Engineering.

Atthe Sudha Gopalakrishnan Brain Centre in Chennai. (Express photo)

“Mohan not only bought the idea, he owned it. He was very confident that it could be done, and convinced that it should be done,” Mitra says.

Sivaprakasam, or Mohan as he is known to everyone, had already built a reputation of managing large and complex projects. In 2011, he set up the Healthcare Technology Innovation Centre (HTIC), a med-tech innovation project that is one of IIT Madras’s most successful ventures. It helped that Mohan had a sound understanding of technology, connections with the industry, and an ability to navigate the bureaucracy. Thanks to running HTIC, he was also networked with doctors and hospitals, a relationship that was to prove useful when the centre needed to procure post-mortem brains.

Mohan and Mitra found support from some other colleagues, and also from Bhaskar Ramamurthi, then director of IIT Madras, who was enthused by the possibility that the computing and other infrastructure created for the project could have collateral benefits for other research areas as well.

A project of this nature required large sums of money, and IIT Madras decided to explore both government and private sources.

In August 2018, Ramamurthy wrote to K VijayRaghavan, then Principal Scientific Advisor to the government of India, requesting if Mitra could meet him to discuss the project. The matter had already been discussed with Gopalakrishnan, who was open to supporting the project, but needed an independent assessment. Incidentally, he too reached out to VijayRaghavan for advice.

“I have always been very keen that Indian science should be making contributions at the global level. The idea of a brain centre held that promise. But I needed some validation. So, I ran it through Vijay whose advice I really value,” says Gopalakrishnan.

VijayRaghavan had taken over as PSA just a few months earlier, after serving as Secretary, Department of Biotechnology, for five years. As PSA, he was expected to provide the strategic vision for Indian science and facilitate policy-making relevant to India’s future needs. The proposal from IIT Madras seemed like just the right idea for him to begin making a difference in his new role.

“It was a daring proposal, very audacious. An engineering department of an engineering institution was trying to make an intervention in biology and do something valuable at a global scale. It was terrific,” says VijayRaghavan.

He spoke to the Prime Minister’s Office about the suitability of the project, and secured a seed funding of about Rs 30 crore. He then set up an advisory committee of scientists to guide the project.

Vidita Vaidya, a leading neuroscientist at Mumbai’s Tata Institute of Fundamental Research (TIFR), was one of the scientists on that committee. “I remember it was during the pandemic that I received an invite from Vijay asking me to join the advisory committee. Frankly, my initial reaction, and that of some other colleagues, was that of surprise. We had never heard of Mohan and his team. It is not like IIT Madras had any major footprint in neurosciences. But since it was Vijay who had put this committee together, we began attending.”

However, it wasn’t long before the scepticism turned into excitement, Vaidya says. Over a series of online meetings, the team at IIT Madras unveiled its plans in detail while seeking inputs and guidance from the advisory committee.

“I was very impressed with the work done by Mohan and his team. Mohan had meticulously figured out the logistical and engineering elements, including the technologies that needed to be developed. Very often, scientists in India are asked to scale down the ambition of their project because it is considered too risky. Here, it was the opposite. We were aiming to build a best-in-class institution, the kind of project that seems possible only in the rich and advanced nations with very large investments,” says Vaidya.

“At one point of time, I remember telling someone that I wanted to get off the committee and begin collaborating,” she says. Vaidya is now working on a joint project with SGBC.

Peering inside the brain

Mohan, designated as the head of the centre, had to start by procuring donated brains of dead patients. At the centre, these brains were cut into extremely thin slices, no wider than a few microns (millionth of a metre), after which very high-resolution images were taken of each of these slices.

An adult human brain has to be cut into 10,000 slices, each about 10-20 microns thick, to get cellular-level details. The slices need to be stained with specific chemicals so that their features can be observed clearly. The computer images then need to be digitally reconstructed back into a full brain. It takes about four to eight months to map one adult brain, depending on its size.

There were several steps in the process that had never been done before, for which new tools and techniques had to be developed. For example, large brain slices, roughly about 6×8 inches in size, cut so thin, were extremely fragile, and could easily disintegrate. Damage to any one of the thousands of slices could render the entire brain useless. Solutions had to be found to handle them safely.

Despite all the precautions, slices usually undergo slight distortions around the edges, making it difficult to digitally reconstruct the brain. Special distortion-correcting algorithms had to be developed to get around the problem.

Then, there was the question of storing all the data that would be generated. The digital image of each slice uses up to 150 GB of data. Imaging an adult brain thus results in a petabyte scale dataset, something that would require at least 1,000 standard laptops to store. Large computers had to be bought and installed, and special computer programs had to be written to organise, search and access this data at a fast rate.

“Several leading experts from more than 25 institutions have worked selflessly to make this happen. People with different skill sets and domain expertise have contributed. That’s the only way a world-leading science mission can succeed,” Mohan says.

These are early days at SGBC, but a huge database has already been created. The centre processes about 10-12 brains at any given time and, on an average, two brains get completed every month. The centre has a pipeline of about 400 brains, stored on campus and in different hospitals in Chennai. This year, the centre plans to release at least three new datasets.

“I have no hesitation in saying that in the kind of work that SGBC is doing, it is ahead of everyone else in the world. It is ground-breaking… a potential game changer,” says Gopalakrishnan.

He has reasons to be satisfied. Gopalakrishnan has so far pumped in about Rs 800 crore into various ventures in Indian science, primarily into brain research at IISc, IIT Madras and a few other institutions. He says he does not have an exact figure for the amount that went into setting up the brain centre at IIT Madras, but has made a long-term commitment.

“I have made it clear that I will continue to support the centre for at least 10 years, no questions asked,” he said.