Interview

‘Every day is a new journey’

Vijayalakshmi Ravindranath is one of those lucky few whose calling is their passion. A neuroscientist of rare distinction, she belongs to an elite band whose work may seem esoteric to the layperson but that, rather than dimming her accomplishments, serves to highlight them.

Founder director of the Centre for Brain Research at the Indian Institute of Science (IISc) in Bengaluru, Dr Ravindranath got her PhD from the University of Mysore before going on to complete her postdoctoral training at the National Institutes of Health in Bethesda (Maryland, USA). Following a spell at the National Institute of Mental Health and Neurosciences in Bengaluru, she helped establish the Gurgaon-based National Brain Research Centre (NBRC), an autonomous central government institution, and moulded it into a hub of excellence.

Currently involved in research devoted to understanding the molecular mechanisms underlying neurodegenerative disorders such as Alzheimer’s and Parkinson’s, the 65-year-old Dr Ravindranath opens up on a range of issues in this interview with Christabelle Noronha.

Vijayalakshmi Ravindranath

What drew you to neuroscience as a career and when did you realise that this was the field of study you wanted to pursue?

I actually graduated with mathematics and physics and did my masters in organic chemistry. I dropped biology in middle school. For my PhD I studied an interesting problem in chemistry with biological significance. That’s what drew me to biology.

Once you start understanding how the brain works and performs, it becomes a fascinating voyage from which there is no coming back. Besides, brain research brings together so many domains — mathematics, computation, biology and, of course, chemistry. I had a steep learning curve and I’m still learning. Every day is a new journey because you are learning new things about the brain and how it functions.

The enormous burden of brain disorders, in India and elsewhere, is distressing. You see people with mental illnesses suffer but they can’t even articulate their pain. There isn’t much empathy for them because of the stigma attached to mental disability and there are no cures for most brain disorders. I felt this was where I really wanted to make a difference. I have been often asked why I am still working at this age, but I am very clear — this is a great opportunity to make a difference.

Are brain disorders genetic?

Some are. Throughout our lives we have almost the same number of neurons we are born with. The nervous system’s development is the first to start and the last to end. Mutations that occur in most genes will affect the nervous system. We believe that mental illnesses have a genetic component and are overlaid with the environment. These together cause the problem. That means multiple genes and multiple environmental triggers.

Because we don’t understand how the disease is caused, we are not able to treat it fundamentally. All we end up doing is provide symptomatic treatment, and this is what we do with almost all mental health problems. We are only controlling the symptoms, never reversing what led to them in the brain function.

Once you start understanding how the brain works and performs, it becomes a fascinating voyage from which there is no coming back.”

Is dementia a cluster of all of these related brain disorders?

Yes, dementia is a set of symptoms that affect our cognition and it can be caused by a variety of factors. As for Alzheimer’s, there is a lot of accumulation of several different kinds of proteins. Normally, proteins are turned over (modified proteins are broken down and new ones synthesised). The more we probe, the more we realise that with age the brain becomes unable to deal with this turnover, and hence proteins tend to accumulate. The dementia that we commonly see is of a mixed kind where multiple factors contribute to the overall syndrome.

Our neurons don’t multiply; the neurons we are born with are what we die with. New neurons are formed but in very small numbers. Somewhere with age our ability to turn over these proteins decreases. So our ability to break down the proteins and clean them away also decreases, causing accumulation. The accumulation is not the cause of the disease, we know that, but the protein clearing is affected as we age and that enables the disease to advance.

We believe that the brain works on a simple principle — ‘use it or lose it’. The more we use the brain, doing more challenging tasks, learning new languages, new skills and forming new connections, the more it helps. If one withdraws from everything and spends a sedentary life without mental stimulation, those connections will wither away. It’s a natural deterioration of the brain. It’s important that as we age we continue to engage with and learn new skills. Mindfulness is a good way to make sure we are attending to things.

You helped establish NBRC in 1999. What did the centre set out to accomplish and has it been successful?

The Indian Institute of Science was the perfect place to establish a neuroscience centre, says Dr Ravindranath

This was the first centre for brain research in India. When I was given charge of the institute, the first goal was that it should act as an apex coordinating centre for brain research in India and, two, that it should have a unified approach to understanding the brain. I believe strongly that complex biological systems cannot be understood without the rigour of mathematics and computation. What was easy to discover has been discovered. What we have left are very difficult things to discover.

I started putting the centre together by hiring people from different domains to bring together a diverse set of talent. We realised it was impossible for us to get an affiliation with a university to award PhD degrees so, in 2002, I went to the government to apply for the centre to be granted the status of a university, which the government did. That gave us the chance to recruit computer engineers, radiologists and specialists from other streams and give them a neuroscience degree.

NBRC was the first neuroscience research centre in India. Today our community has definitely grown and I feel that the centre has played a big role in making that happen. A lot of students who graduated from NBRC went abroad and have come back as faculty. Now, with that unified approach that we had, there is a much more active and lively neuroscience community of younger people.

How important, from a professional perspective, was the return to IISc in 2009?

I gave 10 years to NBRC. The director’s job, especially that of a founder director, was not easy. There was a lot of stress and my own research suffered. I felt I should return to my research and also felt it’s good for the leadership to change in institutions. I informed the government about my decision to leave NBRC, and this was without having a job. Padmanabhan Balaram, the former director at IISc, asked me if I would like to set up a centre for neuroscience. It was an absolute joy because if you want to set up a neuroscience centre there can’t be a better place than IISc, with its strength in engineering and mathematics.

Are you still working with nonhuman primates in your lab?

I don’t work with primates but other researchers do, because primates are closest to humans. We completely renovated the primate centre at IISc and modified it such that we could use it for neuroscience experiments. We have one of the best centres in the country, equivalent to any similar European centre. Primates offer us useful insights on the brain. I also work with mice; we can introduce human genes in them and produce the same symptoms of disease.

How far has India come in neuroscience research, and the outcomes related to such research, since you began your career?

Hard to say because, worldwide, the inputs into neuroscience have been enormous. The 1990s were designated the ‘decade of the brain’ by [then American president] George Bush Sr. This led to a spurt in funding and a remarkable rise in neurosciences around the world. Understanding the burden of disorders, people started setting up huge centres for autism and Alzheimer’s, especially in the United States, where they were able to lure researchers working in other domains of science by giving them huge research grants.

If you look at per capita productivity in science, India is on par but we are still a very small group of neuroscience researchers. In America, for example, the Society for Neuroscience meets every year and 30,000 people attend it. There are 12,000 to 14,000 presentations made there. Here, the Indian Academy of Neuroscience’s annual meet is attended by fewer than 300 people.

The future in neuroscience belongs to people who can bridge different disciplines. We have, somehow, failed in India to develop mega biomedical research projects, which is where the world is going. Biology is too complex to be attempted by a few individuals alone (in the United States this was done by awarding large grants to multidisciplinary research groups). The same applies to cancer research; we need to have big projects. Then huge data sets can be generated, computation experts can analyse the data and large-scale studies of people can be done. That is what we need considering our large population and the burden of disease we carry.

Tell me about the research study you are doing on Alzheimer’s at IISc. What is special about the study?

We believe that the brain works on a simple principle — ‘use it or lose it’. The more we use the brain ... the more it helps.”

Alzheimer’s and related dementias (AD) are a group of devastating age-related brain disorders that affect our memory and other vital cognitive functions that define us as humans. Although AD is essentially a disease of the ageing brain, recent research has indicated that the initiation and slow progression of the disease begins two-three decades earlier. Research on AD at IISc is focused on studying the earliest changes that occur, the idea being to develop rationale therapies that can delay the onset and/or slow down the progression of the condition.

We are doing these studies at two levels. Traditionally, research is carried out in reductionistic systems (cells/animal models) and the insights are then translated to humans. However, such an approach has failed to result in treatments for AD. In fact, in the last decade expenditure of over $15 billion has not yielded a single drug. Our strategy is to carry out longitudinal studies in ageing human subjects; this encompasses a variety of tests.

Through these studies we will be able to identify the risk and protective factors in our population. They will inform our intervention strategies and reduce the burden of dementia. The Tata longitudinal study of ageing is the first of its kind in the country and we hope to continue this for several decades [the study is an initiative by the Centre for Neuroscience and IISc with support from the Tata Trusts]. In our vision, these studies could be a landmark for dementia in a manner similar to the Framingham studies that changed the way we treat cardiovascular disease.

Another unique aspect of AD research at IISc is that these studies on human subjects are dovetailed with experimental studies in mouse models to identify early molecular changes. Our research has shown that changes occur at one month of age in AD mouse models, while the overt disease is seen only at seven-eight months. Also, women are affected more by AD and this is now being modelled in mice with a view to understand the gender difference.

Researchers at the Centre for Brain Research at the Indian Institute of Science