Sandhya’s gusto for guts and affirmative action

WHO? Sandhya Visweswariah, 61

WHAT? Biochemist

WHERE? Indian Institute of Science, Bengaluru

“In a higher administration in the country, there is still an old boys’ club. When they think of someone [for a job], it will be a man; very rarely do they think of a woman being able to do the job. They don’t see us in their boys’ club,” said Sandhya Visweswariah, one of the few women on top in Indian science today.

Sandhya is internationally recognised as a world expert in gut disease. She chairs two biological research labs at the Indian Institute of Science in Bengaluru and has received several grants, fellowships and awards from the likes of The Royal Society and Bill & Melinda Gates Foundation. She is currently the only female grantee of WellcomeDBT India Alliance’s most prestigious Margadarshi fellowship and recently became a fellow of The World Academy of Sciences, for the advancement of science in developing countries.

One of the highlights of Sandhya’s long, illustrious journey is her serendipitous discovery of gut disease-causing mutations. As she won international acclaim for her scientific work, back home she successfully negotiated her way through the proverbial glass ceiling that keeps women from rising to power.

Sandhya, who said she was “never discriminated against nor favoured for being a woman”, suspects that the gender gap in Indian science is a result of “a mindset which may need to be changed.” Her mild and careful approach to the cause of women in science strikes a contrast with contemporary feminism that resists patriarchal power head-on. According to her, the male-dominated leadership holds an “unconscious bias” and fail to take affirmative action to include women in faculty positions, institute leadership and award nominations. “All things being equal, I think they should positively select a woman. That may not be happening,” she said.

“Generally, men are a little more aggressive,” said Sandhya, “for example, when it comes to awards or recognition, they will go and tell a senior person: nominate me. I personally cannot and have never done that,” she said, during an interview at the International Congress of Cell Biology at Hyderabad, earlier this year. She was at the conference to discuss her breakthrough work on a diarrhoea-linked molecular receptor in the gut. Additionally, she also participated in an outreach event where she pushed for science careers in local schools, an experience she told us about in a separate video conversation.

What can we do to close the gender gap, I asked her. “Not much, actually, and the reason is, if you start making a big noise, you are considered a feminist and then you become strident and they avoid you. They don’t want to talk to you after that, right? It’s very difficult,” she rued.

Like other women scientists, Sandhya has found herself in the position of the “token woman” in various committees. “It isn’t enough to have just one woman. In a committee of 10 people, you must have at least three, only then will change happen.” She cites a good example of the European Molecular Biology Organisation, who insists on 30 per cent of women in every scientific meeting they organise.

“If you happen to be a member of an organising committee, you must try and ensure [that more women are included].” This is something Sandhya has tried to do at IISc. She chaired the Women’s Cell for a while and Women in Science panel at her institute. Recently, she lobbied to institute a policy at IISc that pauses the tenure clock of women researchers by one year for every child. Now, women faculty at IISc who are new mothers can apply for tenure on the backs of their publications in the last six years, or seven years in case they had two children, rather than at the end of five years like their male colleagues. “I also ensured that when they do get tenure, it is back-effected [with respect to payrise and position], so it is not that you are one year behind the male colleague. Just because you give her tenure later don’t put her one year behind a male colleague who joined at the same time,” Sandhya explained.

Critique of policies directed at bringing back women after maternity breaks argue that these policies reinforce the stereotype of the sacrificial Indian woman. But Sandhya insists that these are affirmative actions that are the needed in the wake of realities of many of her female colleagues.

In this video by Deccan Herald, Sandhya talks further about her views on women in science in India. https://www.youtube.com/watch?v=Yd5GwPg6gxg

From music in the UK to science in Zambia

Sandhya was born in the UK. As a little girl, she claims she had absolutely no interest in science or research; literature, music and art were more to her liking. When the family moved to Zambia, things changes. “I was 16. When I reached Zambia none of these opportunities to learn music and languages were available. And so I had to completely switch my direction. I had to take up science.” She pulled herself together and got the job done quite well. She stood first in the country. “I got a CGPA of 6 out of 6.”

This is when Sandhya did some soul-searching. “Nobody in my family threw any cold water on the thought.” Despite this global upbringing, she and her siblings were constantly reminded that India was their “real home”. Her options were open and medicine was on her mind.

Influenced by her now late-uncle, a medic and Director at National Institute of Nutrition, Sandhya grew a desire to study medicine. “I could have taken up medicine without any effort in Zambia, but I wanted to come to India,” she recalled. But in India, medical schools at that would not accept her international report cards, they required Indian grading systems.

Sandhya moved to Hyderabad to graduate in science at Osmania University and ended up with a gold medal in botany. Around this time, she met her husband, an air force engineer. “Of course, as soon as you get married, you think ‘oh! my life is complete’ and everything is hunky-dory,” she fondly reminisced. “But my husband said ‘nothing doing. You better find something to do with yourself because I don’t think you’re the kind of person who can sit at home and cook’.”

She tried her luck at IIT Kanpur, where her husband was headed to further his education, and to her surprise, was offered a place there too, to pursue a Masters in the Chemistry department in 1978. According to Sandhya, “It was IIT Kanpur that really showed me what science could be, what education could be. The chemistry department at that time was the best in the country and maybe one of the leading chemistry departments in the world. CNR Rao had just left the year I joined. We had amazing teachers and I think that is when I suddenly realised that I am enjoying this way of working.”

By 1980, Sandhya was deeply tuned to the chemistry of living things. She majored in Biochemistry and went on to pursue a PhD at IISc, which she calls “the best place to do scientific research in the country”.

Post-PhD, she took a year off for pregnancy, but she was lucky that upon her return, she did not have to look very far to find a job. AstraZeneca, a pharmaceutical company, had opened its research division right next door to IISc. “At that time, AstraZeneca was a research pharmaceutical company and had decided that we would target diarrhoeal disease, malaria and tuberculosis.”

The focus, in the beginning, was mainly on diagnostics but Sandhya’s eye was on basic research. She was keen to understand the mechanisms underlying pathogenesis. For a biochemist, signal transduction, or the molecular cascade leading up to the disease state, presents a goldmine of potential discoveries. The conditions were ideal, the stage was set. “Back then, they were flooded with money. I was exposed to technologies which I never would have in a regular Indian university,” she said. Sandhya spent four fruitful years at the company, but beyond that, she realised that industrial/pharmaceutical research wasn’t her ultimate calling.

Meanwhile, at IISc there was a new biochemistry department being set up by Sandhya’s PhD advisor. There was an opening where Sandhya would fit right in. For Sandhya, rejoining the institute in 1993 was the best thing that could have happened. This time, she brought with her the progress she had made in diarrhoeal diseases at AstraZeneca. “The company allowed me to take all the stuff I had done there with me to the institute.”

Discovering disease-causing receptor mutations

“I like to think of proteins, understand how they fold and how they move around,” Sandhya said. The protein fold she knows the best is a molecular receptor in the gut called guanylyl cyclase-c (GC-C). This receptor is a binding target for a family of bacterial toxins that is the major cause of childhood diarrhoea and travellers’ diarrhoea.

Since joining IISc over 20 years ago, Sandhya and her research team have done extensive research on characterising this receptor to understand how it is used by the toxins to cause gut diseases. They also have gathered clues about how its function is regulated by our genes – she did this by introducing mutations in the genes coding for it. She also looks at its other roles and effects in the intestinal cell.

“We were able to show that GC-C regulates intestinal cell proliferation, which meant that it is also involved in the induction of colorectal cancer. Mouse models which did not have this receptor in the gut were more susceptible to tumours.”

The most important discovery in gut biology made by Sandhya and her team was a congenital disease of watery diarrhoea due to mutations found in this receptor. She narrated how this happened. A few years ago, Sandhya heard from clinicians in the University of Bergen in Norway – where she is now Adjunct Professor – about a clinical case of a 32-member family who had suffered from watery diarrhoea from childhood onwards. “There were no diseases reported that correlated with mutations in this receptor that I work with. What was enigmatic [before discovering the Norwegian clinical cases] is how come this receptor is so highly conserved. What is it that makes people not have any kind of mutations in the protein sequence? But then, we heard from these Norwegians who found a mutation. Because it was a nice [co-operative] family they were able to do classical genetic analysis to identify where the mutation lies.”

With the help of Sandhya’s laboratory investigations, the Norwegian clinicians were able to identify the biochemical consequences of this mutation in the receptor that the family expressed. “I knew nothing about them at the time. They wrote this letter, and I said yes, I would be delighted to help. I had a student make the mutation, and we together we found that it resulted in hyperactivation of the receptor.” The hyperactivation of the receptor almost mimics what happens in the gut when the diarrhoea toxin binds to the receptor. That is why these people had lifelong diarrhoea. This was the first report of a mutation in this receptor associated with human disease.

“We named this disease familial diarrhoea syndrome,” said Sandhya, but they soon had to rename it.

Subsequent to the publication of this discovery, Sandhya heard of another clinical case – this time medically more severe. “I received communication from Austrian clinicians, who came to me with four additional mutations in very sick children.” She saw that these were not familial but germline mutations that the infants had acquired randomly. Their parents were perfectly normal, but the infants had been in and out of gut surgery, could not retain food orally and were dependent on injected nutrition.

“We characterised the mutations in the children and what was really freaky was that one of the mutations was exactly the same one we had made [previously as part of laboratory experiments] purely from our biochemical curiosity in this receptor. When I saw the human mutation, it sent a chill up my spine,” she said.

“We are going to now call it congenital guanyl cycle associated disease.”

Sandhya’s most recent work involves using transgenic mice models with this mutation to understand the molecular basis of the rare disease. The hope is to find a cure.

Future plans: Joint PhD-MD at Medical Research Hub

Sandhya with her colleagues at IISc Source: IISc Website

Chancing upon such a discovery hugely widened Sandhya’s perspective on research and disease biology in general. The work biologists do could save many lives if applied well, she realised. “Bioengineering and other innovations in biology are all fine, but we need clinical partners for bringing our research into healthcare.” Such a collaboration between researchers and clinicians is missing severely in the Indian context, in Sandhya’s point of view.

Sandhya and her colleagues at IISc and CMC are preparing a bridge between research and clinicians, called Medical Research Hub. The striking feature of this collaboration is a novel MD-PhD program. “MD students in CMC Vellore will be offered the opportunity to continue into a PhD with faculty at IISc,” she described. During their MD, the candidates will be able to visit IISc several times to define the subsequent PhD project. The costs of these visits are covered by the Margadarshi fellowship that Sandhya has received for a period of 5 years.

“We recently had a meeting with cardiologists from CMC Vellore, four or five of them came to the institute, gave talks, we had engineers sitting in the audience, bioengineers, chemical engineers and materials engineers. They got talking and they are going to start taking a few projects off the ground,” she said.

The Medical Research Hub is an offshoot of Sandhya’s strong belief in positive action that challenges the status quo. Non-men must participate in this change, she strongly believes. “I think affirmative action statements will make a difference. But when the decision making is left to only men, men will engineer [their agenda]”

This is part of a series of  profiles of Indian women scientists whose research has been funded by Wellcome Trust/DBT India Alliance. This article was first published on Firstpost. We are thankful for a grant from India Alliance towards this series that has allowed us to invite voices of fellow science writers on this project.