Meet two scientists who will receive the Infosys Science Prize next week

One is working to find answers hidden in the cell. The other is trying to understand how the brain computes

I magine a blood test that tells you which diseases you could get in the future even before they manifest themselves through symptoms. That is what Yamuna Krishnan, a 43-year-old chemistry professor at the University of Chicago in the United States, is working towards.  

Krishnan is one of the six scientists who will be awarded the 2017 Infosys Science Prize on January 10 in Bengaluru. The award includes a cash prize of Rs 6.5 million and a 22-karat gold medal given by the Infosys Science Foundation that honours outstanding achievements of contemporary scientists across six categories: Engineering and Computer Science, Life Sciences, Physical Sciences, Social Sciences, Mathematical Sciences and Humanities. An independent jury of eminent scientists in each of these fields selects winners from a pool of nominees based on the world-class research they have done. Krishnan won the prize in Physical Sciences.

In Chicago, Krishnan is advancing the pioneering research she led as a Fellow “E” (equivalent to a junior assistant professor) at the National Centre for Biological Sciences, or NCBS, in Bengaluru. In 2009, she discovered a novel method that could potentially test diseases even before they manifest, using nano-devices. Her team cut specific parts from the DNA — our hereditary material — and glued them together to make these nano-devices. So small are these devices that about 10 billion of them can fit in the full stop at the end of this sentence.

I sat down with Krishnan, who was in India for a vacation in December last year, in the new building of NCBS facing sprawling lawns to understand how these nano-devices work.

Krishnan programs these devices that look like little rods to go to a particular location inside a human cell. “It is almost like you can write an address on these nano-devices and give them a map to find a specific location,” Krishnan told me. After finding the address, these devices measure the level of certain chemicals present there, and that tells what diseases one is predisposed to. Between 2009 and 2014, when Krishnan left for Chicago, her team kept fine-tuning the technique.

Krishnan, who grew up in Chennai, took chemistry as a compromise at Women’s Christian College in the city. She found math too difficult, and thought that physics at some level is math, and biology is too much of memorising. The programme in arts wasn’t very enterprising. That left her only with chemistry. But within six months of starting college, she fell in love with the subject. “I really enjoyed it,” Krishnan told me.

Elaborating the technique, Krishnan said that she puts fluorescent detectors on the nano-devices before sending them to a specific location called lysosomes, one of the many organelles inside a cell. Each organelle does a specific job. Lysosomes are like many stomachs of a cell because they digest obsolete and damaged parts of a cell, recycle them and help the cell self-sustain. The nano-devices report the level of chemical ions inside lysosomes by glowing in particular colours. For example, a specific ratio of red and green colour tells about the level of chloride, and a certain ratio of blue and magenta tells the level of sodium inside the lysosomes. A particular ratio of particular ions is like a signature of a specific disease.

Lysosomes can go bad in about 70 different ways, most leading to rare neurodegenerative diseases that especially affect children. By the time these diseases manifest themselves in speech defects, balance problems or wayward eye-movement, “the game is lost,” said Krishnan. “The child [then] has very little time left to live. That is precisely why these diseases need to be caught before they manifest,” said Krishnan.

Yamuna Krishnan, chemistry professor at the University of Chicago in the United States

One in every 5,000 children is believed to have some kind of a lysosomal disorder but that figure is of developed nations, which is where these diseases were earlier thought to be present. In the last couple of years, these diseases have also been reported in developing countries, including India, but there are no estimates. In May last year, Krishnan read an article in a Malayalam newspaper that said there are about 200 children suffering from these disorders in Kerala alone. “So, there might be many more,” said Krishnan. The problem is that there is little awareness about lysosomal disorders in most parts of the world. There is no cure for most of them, and no easy way to diagnose them.

That is why Krishan left NCBS for the Chicago University. To develop a diagnostic test, she needed an interdisciplinary environment and access to cohorts of children with lysosomal defects, which weren’t available in India. In Chicago, Krishnan has co-founded a company called Esya, which in Sanskrit means “to medically examine”. She is in the process of raising seed-funding to develop the test that she wants to make available across the world. “Things are looking good,” said Krishan who plans to put the Infosys award money into Esya.

Development of the test is the first step to getting to the treatment or drug discovery. “If you don’t have quick, easy and efficient ways to not just diagnose a disease but also have a way to track its progression, you are not going to develop therapies,” explained Krishnan. But the real challenge is to get the pharmaceutical industry interested, given the low profit margins in drugs for rare diseases. Nano-devices could potentially be used for drug-delivery but that is yet to be tested.

In the future, Krishnan hopes to expand the test to diagnose other diseases as well, but her current preoccupation is neurodegenerative diseases in children. That is where the greatest need and potential for change is, Krishnan told me over Skype recently. “The life of a child is a worthy cause.”

A  flight of stairs down from the first floor of NCBS, where Krishnan and I were talking, is the lab of 54-year-old computational neuroscientist Upinder Singh Bhalla. Bhalla has won the Infosys prize in Life Sciences for advancing research on how the brain computes. Computational neuroscience is a relatively new branch of neuroscience in which the brain is understood as an information processing system and thinking as a form of computing.

Bhalla grew up on the campus of Jawaharlal Nehru University in Delhi where his parents were economics professors. Although Bhalla found biology “off-putting” in school because of the way it was taught, he came around to marvel at it during his time at Cambridge University from where he graduated in 1986. Bhalla got hooked to neuroscience while working in the laboratory of American neuroscientist James Bower who did pioneering work in computational neuroscience.

Then, in 1996 he landed at NCBS as an E-level reader (equivalent to assistant professor) and for several years worked on the sense of smell — how it is intimately related to memory, emotions and motivations — before turning his focus to a key aspect of memory, which is how our brain recognises and predicts real-world sequences such as music, movements, or words in this sentence. “There is an emerging realisation that a good part of how the brain computes has to do with how we receive information in sequences,” said Bhalla. “It is an everyday thing that our brain does effortlessly.”

Let’s take the example of navigating through the city traffic during rush hour. Although the traffic seems like chaos on the road, there is a sequence or trajectory you follow — and so do the buses, cars, auto-rickshaws, motorbikes and people around you. Bhalla uses computer models to understand how these real-world sequences map on to our brain. He explains that as you navigate through the traffic, the brain cells or neurons in different parts of the brain pitch in to do multiple things: recall the trajectories that were stored as memory, predict your next move, and also predict the trajectories of buses, cars, auto-rickshaws, motorbikes and people on the road, where they are going and might intersect “to get you to your destination without getting killed”.

Behind Bhalla hangs a computer motherboard that he built while he was in high-school. “So, yeah, I dabbled a bit in hardware as well, and had this real talent of setting fire to all sorts of circuits,” he said with a grin.

In his computer models that resemble brain’s computation, Bhalla can see the trajectories build up along the length of the neurons as we move, talk or hear.  “Understanding how the brain recognises such sequences and patterns, and predicts next steps are key attributes of cognition,” said Bhalla. “This helps us understand how intelligence works.”

Over the years, artificial intelligence has come to figure some of the same principles. Bhalla thinks that a better handle on the brain’s computation could help people design better machine learning, say self-driven cars. However, for Bhalla the real value is in decoding the fundamentals of how the brain computes. “We have to know what is going on fundamentally,” said Bhalla. “I have to make this plug because developments are a result of many, many years of basic stuff [science].”

Krishnan agrees. “Breakthroughs often come from investment in basic sciences and by giving scientists a free rein,” she said. When she started her research, she didn’t know that it will ever have an application. She just wanted to know if parts of DNA could form a structure, and why that could happen. “It was an inane question that almost nobody was interested in except me,” recalled Krishnan. And then, one thing led to another.

Other Infosys awardees 

• Sanghamitra Bandyopadhyay, director at the Indian Statistical Institute in Kolkata, won the prize in the Engineering and Computer Science category. She uses computer algorithms to examine biological data. For example, she has discovered new genetic markers for breast and colon cancer. 
• Ananya Jahanara Kabir, professor of English Literature at King’s College London, won the prize in Humanities for applying critical reading methods to Kashmir's cultural expressions such as sculpture, painting, writing, handicrafts and films to present new ways to understand conflict in the region. 
• Ritabrata Munshi, professor in the School of Mathematics at Tata Institute of Fundamental Research in Mumbai, is chosen in the Mathematics category for his research on the analytic aspects of the number theory that is used to study problems of prime numbers, which are often used in cryptography.
• Lawrence Liang, professor in the School of Law at Ambedkar University in Delhi, got the award in the Social Science category for his research at the intersection of copyright law, digital technologies, media, and popular culture.