Produced for India Alliance in partnership with Enabling Biomedical Research in India through Funding and Engagement

The Wellcome Trust/DBT India Alliance (India Alliance) is a public charity dedicated to building excellence in biomedical science by identifying the best researchers and nurturing them as future leaders in basic, clinical, and public health research.

Fellowships in Biomedical designed to encourage young physicians to which aims to strengthen institutional Science participate in research by exposure to the ecosystems. IRMI will also provide scientific method and inspirational role opportunities to Indian research managers to India Alliance envisions improving the models. To date, 67 young clinicians have receive training and create a network of research ecosystem of India to drive health been trained in two workshops. practitioners for serving broader career innovations and inspire the next generation of development needs. researchers. Opportunities for Interdisciplinary and International Collaborations Making Science Accessible With a commitment to catalysing internationally competitive research, India Finding solutions to the problems of modern Open Research Alliance has successfully steered three types society requires interdisciplinary and Open research ensures the unbiased, of fellowship programs to support researchers collaborative science. India Alliance funds instantaneous, and unhindered flow of at different stages of their career —Early major scientific events, including the Young knowledge produced by researchers, thereby Career, Intermediate, and Senior—under Investigators Meetings, to provide young promoting communication and collaborations. the tracks of Basic Biomedical Research scientists the right platform to meet To keep all of India Alliance-funded research and. Clinical and Public Health Research. researchers from across the country, to openly accessible, India Alliance joined Since its inception in 2009, the fellowship discuss ideas and to forge interdisciplinary Wellcome Open Research and Europe PMC programme has awarded 320 fellowships at collaborations. in 2018. Adoption of the open research policy 93 different institutions in 34 Indian cities. The is bound to improve the relationships between focus is on funding the best people early in India | EMBO Symposia various stakeholders, including that between their careers and set them on a leadership India Alliance and the European Molecular researchers and society. track through a continuous system of Biology Organization (EMBO) co-fund up to engagement and mentoring. three meetings per year in India. These Public Engagement meetings are designed to allow interaction of Capacity Building for Research India Alliance aims to bridge the gap between early to mid-career researchers with leading science and society through public international experts. Global challenges in the Science Communication Workshops engagement events that are designed to context of the life sciences and driving facilitate a dialogue. Since the launch of its Communication skills are important in discovery and innovations using public engagement initiative in 2012, India research. India Alliance has developed and interdisciplinary science are the focal points of Alliance actively organizes events that bring successfully conducted Science these meetings. Since its launch in 2017, this the scientific community and public together to Communication Workshops in three formats: initiative has supported four scientific share, debate, and deliberate on important Pan-India SciComm (a two-day workshop in meetings. which participation is based on a pan-India matters of science, especially human health, which have implications for the society. competition), SciComm 101 (a one-day Africa-India Mobility Fund workshop held at institutions on request), and Additionally, India Alliance Fellows are India Alliance, in partnership with the African encouraged to undertake public engagement Science Communication and Career Academy of Sciences, launched the Africa- workshop (a one-day workshop conducted in activities. India Mobility Fund (AIMF) in 2018. AIMF is partnership with Nature India and Nature Jobs a two-year programme designed to provide at major scientific meetings). These researchers from Africa and India workshops have trained approximately 2500 opportunities for short visits in either direction young researchers from about 100 institutions For more information on India Alliance’s to build and strengthen scientific to date. In 2017, India Alliance also programs and its latest initiatives visit collaborations. In recognition of the fact that collaborated with Nature India to organize www.indiaalliance.org Africa and India face similar health Visualising Science, a two-day workshop challenges, the AIMF initiative intends to that introduced scientists to visual tools and encourage South-South collaborations, methods to communicate their research more improve research capacity, and build effectively. leadership in biomedical research in India and Research Leadership Workshops Africa. Scientists manage people and projects; this Strengthening Research makes leadership skills critical to a successful Ecosystems in India career. India Alliance organizes Research Leadership workshops for its fellows and India Research Management Initiative other young Indian researchers to help them recognize and cultivate their leadership style India currently lacks a well-developed and develop management skills. research management system, which is important for institutions to navigate the high Developing Indian Physician Scientists demands for funding, outreach, and (DIPS) Workshops governance of research. To address this lacuna, India Alliance launched the India Developing Indian Physician Scientists Research Management Initiative (IRMI), a (DIPS) workshops, launched in 2017, are Research Management programme for India, Enabling Biomedical TABLE OF CONTENTS Research in India through EDITORIAL 2 OUR LANDSCAPE OF 37 Editors: Rebecca Dargie, Stephen Pincock, EMPOWERMENT AND Amanda Rider EXCELLENCE Funding and Engagement India Alliance team: Shahid Jameel. Sarah Hyder Iqbal, Banya Kar 4 NEW GROUND FOR A TESTED Art and design: Chandra Pal Singh, Wojtek Urbanek PARTNERSHIP TRANSLATIONAL CANCER The Wellcome Trust/DBT India Alliance (India Alliance) is a public charity dedicated to building Picture research: Madeline Hutchinson, Kate Duncan RESEARCH IN INDIA excellence in biomedical science by identifying the best researchers and nurturing them as 5 A FORCE FOR CHANGE future leaders in basic, clinical, and public health research. PUBLISHING 40 Published for India Alliance in partnership with Nature 10 Fellowships in Biomedical designed to encourage young physicians to which aims to strengthen institutional India, part of Springer Nature. Science participate in research by exposure to the ecosystems. IRMI will also provide scientific method and inspirational role opportunities to Indian research managers to India Alliance envisions improving the models. To date, 67 young clinicians have receive training and create a network of NATURE INDIA research ecosystem of India to drive health been trained in two workshops. practitioners for serving broader career Subhra Priyadarshini A NERVE CENTRE FOR innovations and inspire the next generation of development needs. Chief Editor, Nature India FUNDING AMBITION, FROM THE NEUROSCIENCE researchers. Opportunities for Interdisciplinary T: +91-11-48755813 LAB TO THE FIELD and International Collaborations Making Science Accessible [email protected] With a commitment to catalysing 43 internationally competitive research, India Finding solutions to the problems of modern Open Research 13 RESEARCH HIGHLIGHTS Alliance has successfully steered three types society requires interdisciplinary and INSTITUTIONAL & CORPORATE PARTNERSHIPS Open research ensures the unbiased, of fellowship programs to support researchers collaborative science. India Alliance funds instantaneous, and unhindered flow of Sonia Sharma at different stages of their career —Early major scientific events, including the Young 21 knowledge produced by researchers, thereby T: +91-11 4575 5814, M: +91 9650969959, Career, Intermediate, and Senior—under Investigators Meetings, to provide young promoting communication and collaborations. [email protected] the tracks of Basic Biomedical Research scientists the right platform to meet THE CHALLENGE AND PROMISE OF To keep all of India Alliance-funded research and. Clinical and Public Health Research. researchers from across the country, to openly accessible, India Alliance joined CELLULAR SYSTEMS BIOLOGY Since its inception in 2009, the fellowship discuss ideas and to forge interdisciplinary Registered Office: Springer Nature India Private Limited, Wellcome Open Research and Europe PMC programme has awarded 320 fellowships at collaborations. 7th Floor, Vijaya Building, 17, Barakhamba Road, in 2018. Adoption of the open research policy NAVIGATING THE ROAD TO 2030 93 different institutions in 34 Indian cities. The New Delhi - 110 001, India. 46 is bound to improve the relationships between focus is on funding the best people early in India | EMBO Symposia Email: [email protected] DEVELOPMENT GOALS various stakeholders, including that between their careers and set them on a leadership India Alliance and the European Molecular researchers and society. www.nature.com/natureindia track through a continuous system of Biology Organization (EMBO) co-fund up to 24 engagement and mentoring. Public Engagement three meetings per year in India. These Cover photo: © Getty Images meetings are designed to allow interaction of Capacity Building for Research India Alliance aims to bridge the gap between TRANSLATING KNOWLEDGE FOR A early to mid-career researchers with leading science and society through public international experts. Global challenges in the Connect with us on HEALTHIER INDIA Science Communication Workshops engagement events that are designed to context of the life sciences and driving facilitate a dialogue. Since the launch of its Facebook: /npgindia Communication skills are important in discovery and innovations using THE SEARCH FOR HEALTH public engagement initiative in 2012, India research. India Alliance has developed and interdisciplinary science are the focal points of Twitter: @NatureInd SOLUTIONS MUST BE BROADENED 49 Alliance actively organizes events that bring successfully conducted Science these meetings. Since its launch in 2017, this the scientific community and public together to Communication Workshops in three formats: initiative has supported four scientific share, debate, and deliberate on important Pan-India SciComm (a two-day workshop in meetings. 28 which participation is based on a pan-India matters of science, especially human health, which have implications for the society. competition), SciComm 101 (a one-day Africa-India Mobility Fund workshop held at institutions on request), and Additionally, India Alliance Fellows are CLOSING THE GAP BETWEEN TOO India Alliance, in partnership with the African encouraged to undertake public engagement Science Communication and Career Facebook: /IndiaAlliance MUCH AND TOO LITTLE Academy of Sciences, launched the Africa- workshop (a one-day workshop conducted in activities. India Mobility Fund (AIMF) in 2018. AIMF is Twitter: @India_Alliance WEIGHING THE PARADOX OF partnership with Nature India and Nature Jobs a two-year programme designed to provide at major scientific meetings). These UNDERNUTRITION AND FAT 52 researchers from Africa and India workshops have trained approximately 2500 opportunities for short visits in either direction young researchers from about 100 institutions For more information on India Alliance’s to build and strengthen scientific 31 to date. In 2017, India Alliance also programs and its latest initiatives visit collaborations. In recognition of the fact that collaborated with Nature India to organize www.indiaalliance.org Africa and India face similar health DISCLAIMER Visualising Science, a two-day workshop challenges, the AIMF initiative intends to that introduced scientists to visual tools and This Nature India custom issue is published for encourage South-South collaborations, IMPROVING RESEARCH methods to communicate their research more the Wellcome DBT India Alliance, which retains improve research capacity, and build ECOSYSTEMS effectively. responsibility for all content. Nature India custom leadership in biomedical research in India and VACCINES ARE VERSATILE, issues deliver compelling, relevant, and credible VALUABLE AND VITAL Research Leadership Workshops Africa. science-focused content to a global audience of 54 Scientists manage people and projects; this Strengthening Research influential researchers, industry leaders, policy makes leadership skills critical to a successful Ecosystems in India makers, and consumers. Our custom issues mostly 33 career. India Alliance organizes Research focus on affairs pertaining to science and research in Leadership workshops for its fellows and India Research Management Initiative India, and at the same time are of significance to the other young Indian researchers to help them global scientific community. recognize and cultivate their leadership style India currently lacks a well-developed and develop management skills. research management system, which is important for institutions to navigate the high The Nature India custom issues are available freely for A MODERN CONDITION? TAKING ON AMPLIFYING THE VOICE OF Developing Indian Physician Scientists demands for funding, outreach, and download at www.nature.com/nindia NON-COMMUNICABLE DISEASES INDIAN SCIENCE (DIPS) Workshops governance of research. To address this lacuna, India Alliance launched the India Developing Indian Physician Scientists Research Management Initiative (IRMI), a (DIPS) workshops, launched in 2017, are Research Management programme for India, 10TH ANNIVERSARY

OUR LANDSCAPE OF EMPOWERMENT AND EXCELLENCE

Shahid Jameel

The Wellcome Trust/DBT India Alliance is a fellows. Notably, the relative citation ratio of India community dedicated to building excellence in Alliance-funded publications is considerably higher biomedical science in India. This year we celebrate when benchmarked against national comparators, our 10th anniversary. and similar to researchers in the developed world. Since its founding as a public charity in 2008, When we select the best people, fund them at inter- India Alliance has worked towards its mission of national levels, and engage with them meaningfully, enabling biomedical research in India through they respond by competing well. funding and engagement. It harnessed the strength Our scientific influence can also be gauged by of its funders — the Wellcome Trust, United the accolades earned by India Alliance fellows. Kingdom, and India’s Department of Biotechnology Many are recipients of the Shanti Swarup Bhatnagar (DBT) — and has emerged as a game changer for Prize, which is India’s highest mid-career research biomedical research funding. India Alliance has award. Since they opened up to Indian researchers, adopted a set of core objectives, which include em- India Alliance fellows have been the only recipients powering researchers, bridging gaps in the research of the European Molecular Biology Organization system, and striving for excellence in the ecosystem. (EMBO) Young Investigator Award and the Howard Hughes Medical Institute International Research EMPOWERING AN INDIVIDUAL MEANS Scholar Fellowship. EMPOWERING THE WHOLE ECOSYSTEM. Moving ahead with the objective of empow- With our commitment to catalyzing internationally ering researchers, India Alliance trains its fellows competitive research, and training researchers for and others to assume leadership roles in the Indian future leadership roles, the India Alliance team has research ecosystem. steered fellowships to support basic and clinical and public health researchers at various stages of their THE ONLY WAY TO BRIDGE A GAP careers. Transparent processes, and generous and IS TO BEGIN. flexible funding are the hallmarks of India Alliance India Alliance recognises gaps in India’s science fellowships. To date, India Alliance has awarded 320 ecosystem pertaining to gender equality, interna- fellowships, and these have continued to be extremely tional and interdisciplinary collaborations, basic competitive, with a funding rate of about 11%. clinical and public health research, science–policy, The scientific influence of India Alliance has science–practice, and engagement with society. grown since its inception. There is a steady rise in Women face career challenges worldwide — a the quality and quantity of publications from our problem that India Alliance addresses domestically

2 INDIA ALLIANCE 10TH ANNIVERSARY INDIAPICTURE/ALAMY

by designing provisions in the fellowships. It is supporting events that are designed to facilitate important to list the problems and put gender chal- dialogue between scientists and society. lenges on the world agenda; it is more important to drive policy changes to tackle the problem. Women EXCELLENCE IS BUILT ON TRAINING, represent approximately 34% of India Alliance fel- TRIALS AND TRIBULATIONS lows, and we are driven to achieve gender parity. Striving for excellence is the driving force of all Finding solutions requires interdisciplinary activities and interventions of India Alliance, which and collaborative approaches. India Alliance aim to improve India’s research ecosystem. We funds major scientific events that provide young encourage diversity, inclusivity, and transparency in investigators a platform to meet researchers from science. We play our role in changing the research across the country and the world, and encourages ecosystem of India by encouraging scientists to collaborations. We also recognize the importance of return to India from abroad, leading to ‘brain gain’. A FLOURISHING international mobility early in a researcher’s career This Nature India special issue considers the SCIENCE and have such provisions in the fellowships. With 10 years of India Alliance. Articles contributed by ECOSYSTEM the pressing health challenges faced by India, the eminent researchers, India Alliance fellows, and DEPENDS ON THE time is now to initiate conversations between basic, staff, it looks at the impact of our programmes and CREATIVE clinical, and public health researchers and encour- interventions, and cross-cutting themes of rele- CAPABILITIES OF age the training of ‘physician scientists’. vance today. RESEARCHERS, A flourishing science ecosystem depends on the While we are immensely proud of this decade of POLICY-MAK­ERS, creative capabilities of the researchers, policy-mak- action and progress, we are aware of the remaining EDUCATORS, AND ers, educators, and society. Strengthening the links unaddressed needs within our ecosystem. SOCIETY. between these entities depends upon communica- None of this would be possible without the tion. At India Alliance, we empower researchers to vision of a few people at DBT and Wellcome, and communicate science, facilitate science communi- the hard work of many others. The faith they place cation, and advocate its necessity. Science com- in us drives us every single day. This celebration munication also includes public engagement that of the past decade is dedicated to all of them – too empowers society to explore, reason, and question many to be named individually, but they know who actions of the research system. Science, after all, is they are. based on doubt, not faith. In these years, India Alliance has moved from Shahid Jameel public understanding to public engagement by CEO, India Alliance

INDIA ALLIANCE 3 10TH ANNIVERSARY

New ground for a tested partnership

K. VijayRaghavan

The Alliance between the Well- nology (DBT), Government of India Alliance and in new areas? come Trust and India’s Depart- India, and the two decided that Here too, it passes with flying ment of Biotechnology, Ministry the Trust and the DBT should colours. In addition the the ‘tra- of Science and Technology is 10 start a joint programme. Their ditional’ laboratory biomedical years old and is moving to its agreement was followed by a sciences, the India Alliance has next phase. This is an opportune year of work, led by S. Natesh broadened into clinical and pub- time to critically examine the and Shailja Gupta, on the Indian lic health. Now, it hopes to move India Alliance so we can take side, and Jimmy Whitworth and into veterinary sciences, and lessons for the future. his team from the Trust. plant sciences. Under its next in- Let us praise the people of The equal partnership carnation the India Alliance will vision who made this possible. between the Trust and the DBT have support from the Trust, It was preceded by the Interna- created the India Alliance which with the DBT contributing twice tional Fellows Programme of the has had an enormous impact as much. Jeremy Farrar, Renu Wellcome Trust, which started on biomedical science. One way Swarup (Secretary DBT) and in 1998 following a discussion to evaluate people and institu- their teams deserve kudos for with the late, eminient molecu- tions is the ‘loss of function test’. this forward-looking step. lar biologist, Obaid Siddiqi, and Without the organisation, would Cynics abound, who be- his colleagues. Professor Siddiqi we have been better or worse off. moan the state of the world, and wrote to Dame Bridget Ogil- There is no question that we are of science, and tell us attempts vie, then director at the Trust, much better off for it and Indian at change are futile. We need suggesting the need for such a science would have suffered such people, only to see where programme. The Trust, under in its absence. At the start, the the quicksand lies. Partnerships, the guidance of Mary Phillips, India Alliance was, wrongly, crit- such as with the DBT and Well- sought Indian researchers, and icized for ‘cherry-picking’ avail- come Trust, skirt this quicksand, those from South Africa, Cana- able talent and (also wrongly) of and by expertise, daring and da, Australia and some eastern making the good better, but not teamwork, make the impossi- European countries, to compete expanding into new locations, ble feasible. The DBT and the for a small number of very Today, the India Alliance’s Wellcome Trust must continue generous fellowships supporting footprint has extended to all to ensure the independence and substantial research. of India and its fellows are a flexibility of the India Alliance, As the International Fellows benchmark for excellence and which both have guarded programme, which was solely daring in science. To this, we steadfastly. funded by the Trust, neared the owe a lot to the trustees from By nurturing excellence, end of its five-year term, the the DBT and the Trust, and to and simultaneously expanding Trust was under a different di- those who have served as CEOs, scientific enterprise in India, the rector, Sir Mark Walport. It was Anuradha Lohia, and Shahid India Alliance sets an example apparent that the programme Jameel, the team at the India to all others similarly engaged would be wound down. Alliance office, and all the com- with taking India forward. During a visit by Sir Mark mittee members and reviewers. to India he held discussions The second way we judge is K VijayRaghavan with Maharaj Bhan, Secretary by the ‘gain of function’ test. Is it Principal Scientific Advisor to of the Department of Biotech- worthwhile having an expanded the Government of India

4 INDIA ALLIANCE 10TH ANNIVERSARY

A FORCE FOR CHANGE

Jeremy Farrar

How the world has changed since the launch of the Alliance’s impressive public engagement efforts. India Alliance. The global financial crisis had not We are living through a golden age. We are not yet taken hold, Barack Obama had not been elected passive observers of history, and science and inno- president, and CRISPR-CAS was an acronym few vation are changing the world. We are more likely had heard of. The world looks very different as to succeed if we work together equitably, and if we we celebrate a decade of this wonderful Wellcome invest in the disruption, and impatience of youth. Trust/DBT India Alliance. These rapid changes The science community can pool resources, collab- underline the importance of equitable international orate across borders, share data and ideas instantly partnerships; their value has never been greater. in ways not possible a few years ago. Policymakers Among our biggest challenges are health, climate can make decisions based on evidence from any- change, urbanisation and inequality, drug-resistant where. A discovery in Mumbai can be developed by and emerging infections, the inexorable rise in the a collaborator in Lagos tomorrow, an innovator in non-communicable diseases, and the best way to Bengaluru can improve a discovery from San Fran- use big data. None of these can be solved without cisco and develop it commercially, roll it out across investment in Science, Innovation and Society. the world and improve the lives of millions. None can be addressed without countries and foun- Just as science and innovation crosses geo- dations working together, investing in young people graphical boundaries, we can break down artificial to disrupt thinking and provide solutions. boundaries between research disciplines. To im- In 2008, the Nobel Prize for Physiology and prove health, we need social sciences to understand Medicine was awarded to Harald zur Hausen, Fran- cultures we are operating in as well as biology, and coise Barre-Sinoussi, and Luc Montagnier for their physical sciences to help us understand disease. fundamental work on HPV and HIV in the 1980s. At the heart of our approach to improving health From that, emerged a vaccine against HPV, which is is supporting hundreds of researchers. I pay tribute being rolled out around the world. Within a decade to those who started this — especially Maharaj of HIV being identified, the pathogenesis of HIV Bhan, and VijayRaghavan from the Department of infection and AIDS had been proven, and a series of Biotechnology Government of India, to Mark Wal- therapies had been developed which transformed a port and Mike Turner, from Wellcome, Anuradha death sentence into a manageable condition. There Lohia and Shahid Jameel, from the India Alliance. remain many hurdles before we reach these goals, As an established and respected partnership, we but they are wonderful illustrations of how invest- can do more than fund people with great ideas. We ment in discovery science, linked with innovation must push ourselves to do more. We can use our and development, has transformed global health. experience, expertise and authority to influence the Indeed, the challenges speak to the third part contexts in which ideas progress, and to make sure of the trilogy — unless we truly integrate Science, they can generate the maximum possible benefit Innovation and Society, advances will be less well for the largest number. We can ensure a diverse and informed and their benefits delayed for the people inclusive environment, we can shift the centre of we hope to reach. With growing mistrust of experts gravity. What we do today is laying the foundation and institutions, growth in agendas, such as the for a better society and better health. For everyone. anti-vaccine movement, there has never been a more important time to engage the societies we are Jeremy Farrar all part of. That is why we also applaud the India Director, Wellcome Trust

INDIA ALLIANCE 5 6 INDIA ALLIANCE INDIA ALLIANCE 7 8 INDIA ALLIANCE INDIA ALLIANCE 9 T.V. Padma

FUNDING AMBITION, FROM THE LAB TO THE FIELD

From the poverty-stricken communities, analysis of multi- MY WORK to public health research and the hinterlands of Gadchiroli, and ple indigenous food sources, and REQUIRES ME TO nuances around it.” tribal Jharkhand, to India’s elite research on food systems in low- CREATE A PICTURE Ghosh-Jerath hopes her institutes, young biomedical to middle-income populations OF THE RICH research could become globally researchers are showing how and in traditional communities,” BIODIVERSITY IN relevant, by providing leads to imagination and an appetite says Ghosh-Jerath. OUR TRADITIONAL address food shortages, mal- for 'risky' science can reap “Food systems research is COMMUNITIES. nutrition, and the challenge of unexpected benefits for some of still evolving and remains a feeding a growing population by the nation’s poorest, and often niche area for nutritionists in developing sustainable solutions. neglected, regions and people. India. It requires a multidiscipli- “Most of the research The Wellcome Trust/DBT nary team, which is the strength frameworks in food systems India Alliance makes this work of my work, as well as the big- originated in the developed possible through fellowships in gest challenge.” world. Adopting those frame- biomedical research, ranging Her research requires flexi- works in the context of devel- from high-level basic science bility — in time, seasonal travel, oping countries would be a real to urgently needed clinical and collection of food items and innovation.” public health interventions. interactions with indigenous Yogesh Kalkonde trained in Importantly, the fellowships offer communities. It demands spon- immunology, and later in clin- flexibility in choice of work, host taneous travel to capture season- ical neurology in the US, but a institution and travel, free of the al biodiversity; improvisation trip back to India in 2007 to see administrative red tape that can of field techniques to assess the the work of the Society for Ed- stifle research in India. nutritional status of vulnerable ucation, Action and Research in Take, for instance, nutrition communities; and interacting Community Health (SEARCH), scientist, Suparna Ghosh-Jerath with them with the help of local an NGO working in Gadchiroli (pictured on opposite page), non-government organizations. in Maharashtra, completely an India Alliance fellow from “My work requires me to create changed his career trajectory. the Indian Institute of Public a picture of the rich biodiversity Kalkonde analysed causes Health, Delhi, who is studying that exists in our traditional of death among rural people the dietary diversity and nutri- communities, by merging tradi- in Gadchiroli and found stroke tive value of indigenous foods tional ecological knowledge with accounted for 14% of mortality. and their potential contributions scientific methods and rigour.” His team at SEARCH wanted to to food security in four tribal “All this demands continu- conduct a cluster randomised communities in Jharkhand, ous support from the funding controlled trial to find ways to including the vulnerable Sauriya organization and an understand- reduce stroke deaths, and an In- Pahariya tribal group. ing of the complexity of this dia Alliance fellowship allowed “My work requires extensive kind of public health research,” them to get started right away. travel to hard-to-reach places she says. “India Alliance appre- Kalkonde says the fellowship to visit these vulnerable native ciates this transectoral approach helped him find his professional

10 INDIA ALLIANCE 10TH ANNIVERSARY SUPARNA GHOSH JERATH SUPARNA

mission. “I decided to use my Jameel, says recent trends IT IS For Rashmi Rodrigues, from training to solve public health towards stricter visa rules and IMPORTANT St John’s National Academy of problems in rural areas of India funding cuts in Europe and US TO NARROW Health, Bengaluru, the fellow- where significant research is can offer India “the opportunity THE GAP USING ship helped align her medical needed to improve community to retain its best young scientists EXISTING specialization in community health,” he says. and to attract excellent ones RESOURCES. medicine, public health and The team aims to control from overseas”. Outreach events epidemiology with her doctoral high blood pressure and dia- and Young Investigator Meetings work on 'mobile health' and betes, two key risk factors for (YIMs) held in India, Europe chronic infectious diseases. stroke, in a rural population in and USA help the India Alliance Rodrigues, who had worked Gadchiroli. The 3.5-year trial spot potential fellows. earlier with mobile phone-based is the first study of its kind in Besides the fellowships’ technologies to support adher- a rural region of a develop- generous funding and flexibility, ence to HIV treatment regimes, ing country, to see whether a researchers are drawn by the is testing whether mobile-phone community-based intervention chance to prove themselves.“It’s video recordings can help can reduce stroke deaths, says the challenge of making a medication adherence among Kalkonde. difference,” says Vaskar Saha, of tuberculosis patients. One of the principal aims the Tata Translational Cancer Employing Microsoft of the fellowships is to attract Research Centre, Kolkata. With research, India’s ‘99DOT’ inter- promising early-career research- outcomes for patients in India vention, which uses missed calls ers from overseas and promote lagging behind the West, it is to monitor patients, Rodriguez 'brain gain'. important to narrow the gap found that some HIV patients India Alliance CEO, Shahid using existing resources, he says. were placing calls to the support

INDIA ALLIANCE 11 10TH ANNIVERSARY

centre to indicate they had taken According to Nitin Gupta their medicine but were in fact (pictured right), of the Depart- throwing it away. ment of Biological Sciences and The discovery prompted Bioengineering at IIT, Kanpur, her to look for a surer way of the highly competitive India checking that the patients had Alliance fellowships “set a high taken their medicine. She found bar” for the quality of research researchers at Johns Hopkins plans. University (JHU) were working Gupta is recording the elec- on the 'video DOT' concept, trical activities of neurons in the which asks patient to take a brains of mosquitoes to under- video showing them taking their stand why some smells attract medicines and send it via an an- and others repel the insects. droid mobile app to the health- The recordings had not been care provider. The JHU app reported before, says Gupta, and did not, however, work on the so the first task was to optimize CRITICISMS ARE at the Tata Institute of Funda- unsophisticated phones owned techniques. SHARED WITH mental Research, Mumbai, is by most Indian TB patients. “The fellowship’s five-year STUDENTS. mentoring two India Alliance Rodrigues says she was able duration and generous financial THAT IS WHEN fellows. He observes that the to develop an app (pictured support allowed me to take on THEY GET TO fellowships’ peer review process below) that worked in the Indi- a project that required the devel- KNOW THAT is a huge plus. “The criticisms an context only because of her opment of new techniques and SCIENCE IS are shared with students. That India Alliance fellowship. The could not be considered a ‘safe SERIOUS is really when they get to know grant also allowed her to test the project’,” he says. BUSINESS. that science is serious business,” application in a pilot study and Cancer researcher, Bushra says Mallik. refine it. “We are now setting up Ateeq, was apprehensive about He is studying how compo- the trial and preparing to launch moving back from the US to set nents in living cells end up in the app, called v.Cure, on Goog- up an independent faculty at IIT, the right place at the right time le Play Store," she says. Kanpur. “With India Alliance with the help of ‘motor proteins’. “Simply stated, I would not funding in hand, my transition The work could shed light on have been able to carry out my was smooth,” she says. This how motor proteins ferry path- work without the fellowship,” was despite Ateeq’s decision to ogens in cells to the lysosome, says Rodrigues. She says it let change her choice of host insti- a chamber where the pathogens her realize her abilities “profes- tute from a well-known cancer are degraded, or conversely, sionally and personally”. research institute to IIT, Kanpur, how some pathogens manage to better known for engineering. escape the lysosome trap. She credits the fellowship “India Alliance fellowships with giving her the confidence are unlike other grants, where to set up a successful research the allocated funds are tight- team that is spearheading basic ly compartmentalized into and translational research in various budget heads and there prostate, breast and colorectal is minimal room for change cancers. Its goal is to understand even if there is a genuine need,” the molecular mechanisms says Gupta. He describes the involved in cancer development flexibility as a “life-saver”, giving and drug resistance, and identify young researchers the freedom targets for potential therapies to put the money to best use for and diagnostics. their project—and realize their Roop Mallik, a senior fellow ambitions.

12 INDIA ALLIANCE RESEARCH HIGHLIGHTS 10TH ANNIVERSARY

The work could improve un- tobacco-chewing and a spread of drugs eliminated bacteria CELLS IN TUG OF WAR derstanding of how the cell cycle tumours to the lymph nodes. It displaying oxidative cytoplasm, Cellullar behavior is controlled in the body. forms the basis for the NOTCH1 whereas bacteria maintaining Abhijit Majumder signalling pathway as a thera- highly reduced cytoplasm were Early-career Fellowship peutic target in tongue cancer. refractory to the drug. Indian Institute of Technology Bombay The study also identifies the Biomaterials Science May 2018 NEW PATHWAYS MMP10 as a potential biomarker Cancer Amit Dutt for patients at risk of developing Classical biology says it happens Intermediate Fellowship metastases. via secreted chemical signals or ACTREC, Tata Memorial Centre, Mumbai vesicles, or at times, by direct Oral Oncol. Oct 2017, Oncotarget August contact. 2016 POPULATION CONTROL Work by Abhijit Majumder, Infectious diseases and Jyotsna Dhawan, showed Amit Singh IMAGES LIBRARY/GETTY SCIENCE PHOTO that two cells may communicate Senior Fellowship by deforming their surround- Indian Institute of Science, Bengarulu The Journal of Biological Chemistry Feb ings. By seeding human Mes- 2016, PLoS Pathogens Jan 14 Tuberculosis bacteria (purple) infect- enchymal Stem Cells (hMSCs) ing a macrophage white blood cell. on soft gel, the team showed if two cells pull the gel in opposite A major obstacle in the clinical Offsetting the acidic pH of directions, the gel effectively treatment of tuberculosis (TB) is infected macrophages restored stiffens locally, in the same way the long therapy time needed to homogeneity in the Mtb popula- a slack rope becomes taut in a clear the infection. A plausible tion. The work shows that it may tug-of-war. As a result, the cells explanation for the disease’s be possible to tackle drug resist- start to behave as if they are on A plot of quality candidate fusions symptoms is the development ance by blocking macrophage a rigid material, and collectively transcripts in tongue tumours. of heterogeneity — whereby a acidity, and by developing drugs override the effect of substrate genetically identical population that generate oxidative stress in stiffness on their functions. Head and neck cancers are com- of Mycobacterium tuberculosis Mtb. mon, and have significantly high (the pathogen that causes TB) death rates. A useful predictive diversifies to produce drug-tol- factor for clinical outcome is erant subpopulations. NEURON REPAIR whether there is regional lymph Until recently, these sub- Neuronal processes node metastasis. This deter- populations were identified Anindya Ghosh-Roy mines the choice of treatment. as rare non-replicating cells Intermediate Fellowship National Brain Research Centre, A study by Amit Dutt, and (persisters) that do not respond Haryana colleagues, has used whole-ex- to anti-TB drugs. But, recent Proc Natl Acad Sci USA. Nov 2017 ome and transcriptome sequenc- studies identified phenotypical- ing of early tongue tumours to ly distinct mycobacterial cells At high density, cells elongate describe fully, for the first time, showing drug tolerance even in Damage to nerve cells can affect towards their neighbour. genomic and transcriptomic actively replicating populations. the ability to walk, see, and alterations. It sought to identify Amit Singh and colleagues, smell. If damaged in adulthood, Both cells sense this local known and novel variants, copy have developed a biosensor to the long projections of injured change of rigidity and extend number alterations and tran- peek inside the mycobacterial neurons, known as axons, are long protrusions towards each script fusions that could play subpopulations in real time. thwarted from finding their other along the locally stiffened a part in early tongue tumours They noted distinct varia- way to their target, and cannot inter-cellular region. This leads and nodal metastases. tions in the level of redox-stress properly transmit signals. to cell-cell connection result- This data, gleaned from experienced by Mtb subpop- In experimental models of ing in a network-like pattern Indian patients, presents the ulations inside the infected nerve regeneration, injured spreading over the substrate. first evidence for a link between macrophages. Further, anti-TB axonal fragments can occasion-

INDIA ALLIANCE 13 10TH ANNIVERSARY RESEARCH HIGHLIGHTS

ally reconnect autonomously. composition and absorption are and ocular fluids at all stages of Using C. elegans to examine the not optimum. Measurement of BETTER VIEW OF RISK the disease, various downstream sensory neurons responsible protein digestibility is critical, Clinical ophthalmology molecules regulated by TGFβ1 for touch sensation, Anindya but since proteins are digested Aparna Rao were differentially expressed Ghosh-Roy’s team found that and absorbed in the small in- Intermediate Fellowship in glaucoma cases suggesting fusion between proximal and testine, it is hard to estimate the LV Prasad Eye Institute, Bhubaneswar altered regulation of these distal fragments of injured neu- undigested remnants of ingested PLOS One 2017 pathways as a possible cause for ron leads to functional recovery. proteins when they have been glaucoma pathogenesis. Axon fusion is achieved by rec- processed. Pseudoexfoliation is a mysteri- An analysis of these ognition of the distal and prox- A team led by Anura Kur- ous ocular disease characterized pathways can identify markers imal ends and mixing of lipid pad, has developed a non-in- by dandruff like deposits in the signifying glaucoma onset and bilayers of both. It is catalyzed vasive dual stable-isotope eye which can lead to glaucoma lead to novel therapeutic agents by a protein called EFF-1. (13C,2H) method with intrinsi- and, eventually, blindness. Due against these molecules. The team also discovered cally labelled food proteins to to the large number of clinical the ability to restore function measure protein and amino acid phenotypes, it is difficult to diminished with age, but found digestion. quantify the risk of glaucoma or MALARIA DRUG REUSED this ability can be restored by Through this method, the blindness associated with indi- Translational cancer research the removal of a conserved RNA digestibility of rice, millet, vidual phenotypes. Such infor- Bushra Ateeq let-7. This self-fusion might oc- legumes, eggs and meat has mation would help identify risk Intermediate Fellowship cur after spontaneous breakage now been measured in adults in the early stages of the disease, Indian Institute of Technology Kanpur of the axonal process because of and children. The digestion of allowing for timely intervention Neoplasia, 2017 stress induced injury. animal source protein is good and monitoring. (~90%), but that of legume and Researchers have shown how a millet protein was much lower World Health Organization-ap- than expected (~60%). This illu- proved malaria drug can be used minates the risk of quality-pro- to treat anti-androgen resistance tein deficiency in cereal-heavy in metastatic prostate cancer. diets, particularly in children. The majority of PC patients An increased diversity of food undergo hormonal therapies intake is needed for optimum that target several nodes of an- nutrition. drogen receptor signalling, such The nematode C. elegans with GFP India should move away The typical three ring sign of ocular as androgen deprivation therapy labeled touch neurons. from cereal-centric food subsi- pseudoexfoliation. or ADT, but most of them de- dies, and put greater quantities velop resistance to treatment of quality foods into the system, Aparna Rao and a team at and progress to an aggressive the authors recommend. the LV Prasad Eye Institute, stage called castrate-resistant GETTING THE MEASURE Bhubaneswar, recently showed prostate cancer, or CRPC. Clinical nutrition glaucoma in 30-40% of earlier To tackle this problem, Anura Kurpad Margdarshi Fellowship pigmentary forms of the disease Bushra Ateeq and colleagues St John’s Medical College, Bengaluru and more than 50% incidence repurposed a WHO-approved American Journal of Clinical Nutrition 2018 of glaucoma in those with com- antimalarial drug, Artesunate, to bined phenotypic variants in the restore the sensitivity of CRPC Protein intake has generally same eye, indicating a need for to anti-androgen drugs. been considered adequate in IMAGES DELIMONT/GETTY DANITA closer follow-up of patients with Experiments using human India, where the dietary energy these clinical variants. castrate-resistant prostate can- is derived largely through They also found that despite cer cells showed that Artesu- monotonous cereal-centred continued overexpression of nate in combination with an diets. While these deliver India should move away from cereal the transforming growth factor anti-androgen drug revokes sufficient crude protein, their food subsidies beta-1 gene, TGFβ1, in serum the cancer-causing potential

14 INDIA ALLIANCE RESEARCH HIGHLIGHTS 10TH ANNIVERSARY

of these cells. Mechanistically This prompted Farah Ishtiaq elevations and compromise the were younger, had poor social the drug combination induces and a collaborator to test wheth- oxygen carrying capacity, and support and mostly gave birth to ubiquitin-mediated proteasomal er infections by high intensity fitness of high elevation birds. smaller babies. degradation of the androgen avian blood parasites such as In contrast to the current receptor, subsequently sensitiz- Plasmodium, Haemoproteus and detection rates in public hospi- ing castrate-resistant prostate Leucocytozoon compromise the tals by obstetricians, the team MENTAL HEALTH LINK cancer cells to anti-androgen oxygen carrying of elevational has proved the feasibility of Maternal health drugs. Combinatorial therapy in migrants’. Giridhara Babu screening for GDM and mental xenografted mice resulted in a Intermediate Fellowship health problems. Screening and regression of more than 95% in Public Health Foundation of India - timely management of GDM IIPH Bengaluru tumour burden and metastases. and mental health in pregnant BMC Pregnancy and Childbirth, 2016 This work provides women can improve the chance compelling pre-clinical evidence of optimal birthweight. that Artesunate could disrupt Higher glucose levels and resistance towards anti-andro- The chestnut-crowned laugh- symptoms of mental distress in gen drugs in patients who don’t ingthrush, an elevational migrant. pregnant women can affect the respond to ADT. Clinical trials birth weight of babies. should follow. The researchers sampled 18 Giridhara Babu and col- species of passerine birds during leagues found that the birth- breeding and non-breeding sea- weight of newborns is influ- sons across seven sites in west- enced by the mother’s glucose Maternal mental health monitoring ern Himalaya for blood parasite level and psychosocial environ- can improve birthweights. intensity and two physiological ment. The results are from a parameters — Haemoglobin birth cohort funded by the India (Hb), the protein in red blood Alliance, wherein, symptoms of cells responsible for transport- mental distress and glucose lev- FINDING RISK PATTERNS Public health ing oxygen, and Haematocrit els were assessed in the second Artesunate-mediated inhibition Jeemon Panniyammakal in the NF-κB signaling pathway. (Hct), the percentage of red trimester of pregnancy. Intermediate Fellowship blood cells in blood. The researchers found that SCTIMST, Trivandrum They found that the proba- one in six women have gesta- J Clin Lipidol, Feb 2018 bility of Plasmodium infection tional diabetes mellitus (GDM) MOUNTAIN MIGRANT RISK decreased with elevation, while and a similar proportion of Infectious diseases Leucocytozoon infection risk women also had symptoms Recognizing family risk patterns Farah Ishtiaq Intermediate Fellowship increased with elevation, albeit suggestive of mental distress. Of for heart attack helps identify Indian Institute of Science,Bengaluru as submicroscopic infections. the babies born in the cohort, and target people who most BMC Ecology, 2018 Parasites persisted in birds with 16.7% were small for their need preventive interventions. high intensity infections during gestational age (SGA), and 9% A study, called PROLIFIC, non-breeding seasons. Parasite were large for their gestational tested the effectiveness and sus- Himalayan migrant birds have intensity had a markedly neg- age (LGA). Women with blood tainability of an integrated care evolved to cope with enviromen- ative effect on Hb and Hct, in glucose levels lower than the model for managing heart attack tal hypoxia, or oxygen depletion, birds with co-infections. established cut-off level for the risk in 750 high-risk families by increasing the production of Elevational migrants are diagnosis of GDM gave birth to in Kerala, comprising 1,671 red blood cells to help carry more exposed to more parasites at low heavier babies with greater fat participants with family history oxygen to their muscles. However, elevations than birds that reside deposits. Women with GDM, of premature heart attacks. The if they become infected by para- at higher elevations, because had a higher risk of having care model involved screening sites that prey on red blood cells, the climate at lower elevations hypertension, depressive symp- for cardiovascular risk factors, their oxygen-carrying capacity is optimal for parasite transmis- toms and undergoing caesarean offering lifestyle interventions, may be lowered, leaving them at sion. But, as global temperatures section. Women with symptoms providing a framework for links risk of anemia. rise, malaria will reach higher suggestive of mental distress to appropriate primary health-

INDIA ALLIANCE 15 10TH ANNIVERSARY RESEARCH HIGHLIGHTS

care services, and follow-up of been reported in hemochroma- in the adult fly, rather all hemo- intervention adherence. tosis (a genetic condition char- cytes originate from embryonic SCRATCHING THE SURFACE The programme lead by acterized by iron accumulation and larval stages. Applied microbiology Jeemon Panniyammakal, was in the liver). Lolitika Mandal and team Jafar Hasan unique for its task-shifting/ asked a fundamental question: Early Career Fellowship sharing strategy of involving if adult fruitfly is incapable of Indian Institute of Science, Bengaluru Scientific Reports, 2017 non-physician healthcare work- producing new blood cells, how ers in managing heart attack does it survive basic threats, risk at the family level. After a such as bacterial infections that Millions die every year from year, the model was effective in demand a swift, spontaneous hospital acquired infections due reducing average blood pressure, An explanation for the link between immune response? In verte- to contact transmission among fasting blood glucose levels and iron overload and insulin resistance. brates, such occurrence is met immunocompromised patients cumulative risk for heart attacks. by different types of blood cells and surfaces. Prone areas The PROLIFIC study initial Research by Joe Varghese and that are routinely regenerated. include surgical sites, bed-rails, findings suggest that lifestyle colleagues sheds light on these Using genetic tools, the call buttons, sinks, toilets and changes are effective when contradictory observations. They researchers found sites on the tables in intensive care units or delivered to the whole family, show that increasing intracellular dorsal side of the fly abdomen hospital wards. as it works within a framework iron in hepatocytes produced where resident blood cell pro- The wings of some insects, of genetic and cultural relation- dual effects on insulin signaling genitors demonstrate capacity such as dragonflies, have known ships. in these cells. On one hand, the for immune responses and antimicrobial properties. Bac- increased levels of intracellular proliferation, after infection. terial cells are killed when they iron activated insulin signalling come into physical contact with in a ligand-independent manner, nanopillars on the wings. i.e., in the absence of insulin. Taking inspiration from Meanwhile, accumulation of iron these wings, Jafar Hasan and in hepatocytes attenuated activa- team have designed an econom- tion of the pathway in response ical method to combat drug Family based approaches influence to insulin, resulting in a state of resistant bacteria on hospital positive outcomes. insulin resistance. The fruitfly sites where blood cell surfaces. By etching multi-scale These findings provide a progenitors respond. topographies on aluminium or plausible explanation for why aluminium alloy surfaces, they iron overload, in general, is as- Blood cells from larval and created a surface capable of TOLERANCE TESTED sociated with insulin resistance embryonic stages migrate to killing a range of drug resistant Metabolic disorders and Type 2 diabetes, and why these sites/hubs in the adult fly, bacteria that had been isolated Joe Varghese Early Career Fellowship improved glucose tolerance and mirroring the post-birth voyage from hospital surroundings. Christian Medical College, Vellore insulin sensitivity are seen in of hemocytes from liver to bone BBA-General Subjects, 2018 hemochromatosis. marrow in mammals. Strikingly, the cells of the hub, like bone marrow resident blood cells are ANNIE CAVANAGH Insulin resistance is a condition enriched in Laminin A and type BONE MARROW PROBE where tissues do not respond IV collagen. Developmental biology adequately to the hormone Lolitika Mandal The researchers are consid- insulin. It is a characteristic of Senior Fellowship ering whether this is a simplistic Type 2 diabetes, and has been Indian Institute of Science Education bone marrow-like arrangement, Drug-resistant bacteria are rife in and Research, Mohali reported to be strongly associat- and whether these hubs could hospital settings. Developmental Cell, 2015 ed with increased serum ferritin shed light on bone marrow levels (a marker of increased hematopoiesis. They hope this They compared the rough- body iron stores). In contrast, Scientists have long believed model will improve understand- ness of the surfaces to the bac- improved insulin sensitivity has that no new blood cells are born ing of blood cell function. terial killing rate and found that

16 INDIA ALLIANCE RESEARCH HIGHLIGHTS 10TH ANNIVERSARY

five roughness parameters in a which leads to activation of the A prominent, but untested, provide care and follow-up for specific range determined the inflammatory arm of the innate hypothesis was that oscillations those suffering from depression, killing efficiency of the bacterial immune system that kills the create periodic windows in anxiety and increased risk of cell. The findings suggest that if engulfed C. glabrata cells. which a neuron collects inputs suicide. SMART was imple- such materials are employed in Consistent with this, the C. from other neurons. With paired mented across 42 villages of one various hospital areas, the trans- glabrata strain lacking proteases extracellular and intracellu- district of the south Indian state mission of hospital acquired is also unable to survive in the lar recordings and controlled of Andhra Pradesh, representing infections can be significantly mouse model. stimulus manipulations in a population of about 40,000. reduced. Collectively, our results awake locusts, Nitin Gupta et al. The project brought in- reveal proteases to be a potent demonstrated the presence of creased awareness and reduced weapon in the anti-host arsenal oscillatory integration windows stigma surrounding mental of C. glabrata, which allows it to in the olfactory system. Then, health issues, but also resulted SURFACE WARRIORS establish successful infections in with a computational model, in huge increases in num- Immune system Rupinder Kaur the host. the authors described how noisy ber of people with identified Senior Fellowship fluctuations in the voltage of disorders seeking help from Centre for DNA Fingerprinting and neurons plays an essential role primary health care providers, Diagnostics, Hyderabad in the creation of those win- from around 1% prior to the Journal of Biological Chemistry 2018 NEURAL WINDOWS OPEN dows. intervention to about 13% over Neurophysiology Nitin Gupta These findings show how the a three-month intervention. A Life-threatening bloodstream Intermediate Fellowship precise timing of a spike with re- year-long intervention at another infections, caused by fungal Indian Institute of Technology, Kanpur spect to the oscillation cycle can site has also led to even higher pathogens, pose a grave health Nature Communications 2016 be an important determinant use of mental health services and risk and cause major economic for the responses of neurons, the results are being analyzed. hardship. Oscillatory neural activity has providing new insights into The community members and Candida glabrata is an been found in nearly every part temporal coding. leaders said the changes were emerging human fungal patho- of the human brain, as well as useful. The results are a solution gen which possesses the ability in model systems. Oscillations for mental health care for remote to survive and multiply in mac- represent the synchronized and disadvantaged communities SMART ROUTE TO CARE rophages, which are paramount activity of multiple neurons in a in low resource settings. Mental Health as frontline representatives of brain region. Pallab Maulik the human defence system. There are good descriptions Intermediate Fellowship Rupinder Kaur and col- of how oscillations are generated George Institute for Global Health, New Delhi leagues have shown that a and behavioral evidence that BMC Psychiatry, 2017 family of eleven cell surface-as- oscillations are important, but sociated aspartyl proteases still little understanding of the (protein-hydrolysing enzymes) mechanisms by which oscilla- Given India’s population and An information campaign to reduce of C. glabrata plays a key role, as tions contribute to information vast area, it is not feasible to stigma about mental health issues. it does not allow macrophages processing in the brain. have trained mental health to mount an intracellular killing professionals to meet needs. response. Using mobile-based technology, Our data demonstrate that the Systematic Medical Ap- ILLUMINATION ON CELLS Membrane biology C. glabrata aspartyl proteases praisal, Referral and Treatment Raghu Padinjat help in keeping the cell surface (SMART) Mental Health Project Senior Fellowship intact and pathogen-associated has developed and imple- National Centre for Biological Sciences, Bengaluru molecular patterns (PAMPs) mented multiple approaches, Scientific Reports, 2018 hidden. including strategies to increase FEBS Lett. 2018 In the absence of proteases, mental health awareness, and these PAMPs are unmasked, and the training of primary care Cells detect changes in their recognized by macrophages, Kenyon cells in the insect brain. health workers and doctors to environment using plasma

INDIA ALLIANCE 17 10TH ANNIVERSARY RESEARCH HIGHLIGHTS

membrane receptors, and their In the brain, neural cells ex- A study by Amit Tuli, and porter channel, called VDAC, ability to respond to stimuli de- press GPCRs (5-HT2a, mGluR Mahak Sharma, has identified in mitochondria. Hence, VDAC pends on the numbers and types and opioid receptors) of critical PLEKHM1 as a novel interaction is dubbed the cell’s ‘governator’. of receptors they express. How importance to brain function. partner of Arl8b that repositions Four decades after its identifi- do cells tune plasma membrane Mechanisms that regulate lysosomes to the perinuclear cation, scientists are still trying receptor composition? their numbers on the plasma location. to understand how VDAC is Rhodopsin, the receptor that membrane instruct the mecha- The authors find that PLE- made and transported, how it detects light, is a prototypical nisms of mental illness, such as KHM1-Arl8b complex promotes folds and functions, and how it G-protein coupled receptor schizophrenia. fusion of the repositioned is regulated. Moreover, the link (GPCR) and its levels are a key These findings on the lysosomes with autophagosomes between misfolding and dysreg- determinant of photoreceptor control of rhodopsin levels at that contain damaged cellular ulation of VDAC and diseases sensitivity. the membrane illuminates the cargo destined for degradation. such as Alzheimer’s, Parkinson’s, In photoreceptors, the regulation of such processes. Notably, mutations in PLEKHM1 and cancer, is unknown. light-sensitive membrane turns gene result in osteopetrosis, a over; during illumination, endo- condition where bones harden cytosis of rhodopsin containing and lead to skeletal deformities. LOCATION, LOCATION plasma membrane is coupled to This study reveals that Arl8b Lysosomal trafficking recycling of receptors back to Amit Tuli and Mahak Sharma* regulates PLEKHM1 localization the cell surface. Intermediate Fellowships on lysosomes, which in turn Raghu Padinjat and col- CSIR-Institute of Microbial may regulate PLEKHM1 func- Technology, Chandigarh leagues have observed that Indian Institute of Science Education tion in bone remodelling. during illumination, the enzyme and Research, Mohali phospholipase D is activated and Journal of Cell Biology, 2017 is essential for coupling endocytosis of plasma mem- Studies have revealed that, in Molecular handles that govern VDAC brane with its recycling back to addition to their traditional role structure and function. the surface. in digestion and waste remov- al, lysosomes regulate diverse Radhakrishnan Mahalaksh- biological processes includ- mi, and her team at the Indian ing plasma membrane repair, Institute of Science Education antigen presentation, metabolic and Research, Bhopal, are un- signalling and cell migration. ravelling these molecular mys- It is becoming increasingly teries governing the governator. evident that subcellular posi- HeLa cells stained for late endoso- The researchers identified tioning is a key factor regulating mal/lysosomal proteins. the molecular elements that these newly-revealed functions control VDAC stability, and of lysosomes. Lysosome posi- showed how the structure of this tioning is regulated by Arl8b, a channel relates to its stability protein that promotes movement CHASING THE GOVERNATOR and function. Drosophila retinae co-stained with Membrane biology Rhodopsin 1, the receptor for light. of lysosomes on cellular high- Most recently, they also Radhakrishnan Mahalakshmi ways known as microtubules. By Intermediate Fellowship identified molecular zones of In the absence of phospholi- recruiting microtubule-based Indian Institute of Science Education this channel that cause aggrega- and Research, Bhopal pase D activity, these sub-cellu- motor proteins on lysosomes, Phys. Chem. Lett. 2018 tion, so are likely to aggravate lar processes are uncoupled. As Arl8b regulates lysosome motility neurodegenerative diseases. a consequence, the photosensi- from the perinuclear region to The finding gets researchers tive membrane shrinks, fewer the cell periphery. This in turn ATP is the energy currency of closer to regulating VDACs in rhodopsin molecules are present regulates lysosome function in all living cells. It is produced the cell, and providing potential and photoreceptors become less plasma membrane repair and cell in mitochondria and is made treatment for neurodegeneration sensitive to light. migration. available to the cell via a trans- and cancer.

18 INDIA ALLIANCE RESEARCH HIGHLIGHTS 10TH ANNIVERSARY

lism is therefore likely to provide be strongly induced by gratings THE FAT CONTROLLER INFLAMMATORY LIPIDS a two-pronged mechanism of of alternating black and white Lipid homeostasis Infectious diseases balancing host inflammatory stripes. In the study the gamma Roop Mallik Sheetal Gandotra responses and susceptibility of oscillations generated by colour Senior Fellowship Intermediate Fellowship Mtb to oxidizing stress. stimuli were even stronger than Tata Institute of Fundamental Research, CSIR-Institute of Genomics and those induced by the gratings, al- Mumbai Integrative Biology, New Dehli Proceedings of the National Academy of Infection And Immunity, 2018, most 10-fold more in some cases. Sciences, December 2017 Frontiers in Immunology, 2018 They found that the magnitude of gamma oscillations depend- ed on the purity of the colour, Excess fat circulating around Lipid droplets, once considered but not so much on the overall in blood leads to diabetes and benign depots of excess fat in brightness. The team related this heart disease. Roop Mallik and the cell, are revealed to be driv- result to a particular mechanism colleagues show how the liver ers of inflammation in tubercu- by which colour signals received controls fat. losis infected macrophages. by the retinal cone receptors are

When we go to bed after Tuberculosis granulomas LIBRARY/GETTY PHOTO GSCHMEISSNER/SCIENCE STEVE processed in the brain. dinner, glucose is in plentiful exhibit an enrichment for Tuberculosis bacteria infecting a supply, but when it’s depleted, neutral lipids such as cholesterol macrophage white blood cell. fat is needed to run the body. esters and triglycerides, which Fat-containing tissues respond are stored as intracellular lipid by sending fat to the liver, droplets. Having found that the which is soon loaded, but still pathogen Mycobacterium tuber- OFF THE COLOUR CHARTS Neuroscience continues to secrete this fat at a culosis could host cell triglycer- Supratim Ray constant rate. This remarkable ides, Sheetal Gandotra and team Intermediate Fellowship Indian Institute of Science, Bengaluru elasticity of the liver prevents investigated the role of the bacil- High-level congnition was recorded PNAS, 2018, dangerous fat overload in blood. li causing lipid accumulation. when red images were shown. Using a guinea pig model of infection and human mac- What changes in the brain when rophages, they identified a role one sees a colourful flower, as for infection induced necrosis in opposed to a grey version of the ASTHMA DEFINED Respiratory disease development of foamy mac- bloom? How do signals change Anurag Agrawal and Tavpritesh Sethi rophages. when looking at a green jack- Senior and Early Career Fellowships Necrotic cells provide lipids fruit versus a red tomato? CSIR Institute of Genomics & Integra- tive Biology and All India Institute of to bystander cells that not only Supratim Ray and colleagues Medical Science, New Dehli utilize lipids for DGAT1 de- studied this by recording signals Journal of Translational Medicine 2017 Cultured liver cells show fat bodies pendent triglyceride synthesis, in monkeys from the primary taken to the cell periphery. but amplify the inflammatory visual cortex, an area of brain response to infection. involved in visual processing, as Advances in genomics and To enable this, insulin gets The study shows that tri- they were shown various natural molecular sciences are help- the motor protein kinesin to glyceride levels in the host cell images. To their surprise, they ing refine disease definitions attach to fat bodies. Kinesin pro- do not affect bacterial growth, found strong oscillations in the and tailor treatments. Such pels fat bodies to the periphery rather metabolic activity of recorded signals at frequencies precision-medicine or ‘strati- of liver cells, from where the mycobacteria in lipid rich con- in the range 30-80 Hz, called fied-medicine’ strategies rely on fat is released into blood. With ditions is higher. This increased gamma oscillations, that are discovery of a disease’s sub-divi- time, fat accumulates in the metabolic activity of M. tubercu- known to be linked to high-level sions, or endotypes. In common, liver, but insulin levels will also losis in lipid-rich host cells was cognition, whenever reddish complex diseases such as asthma diminish. Kinesin now falls off also associated with increased images were shown. and diabetes, which are more from the fat bodies, secretion is resilience to oxidative stress. Tar- In the visual cortex, gamma nuanced, these endotypes are reduced, and all is well. geting host triglyceride metabo- oscillations have been known to harder to discover.

INDIA ALLIANCE 19 10TH ANNIVERSARY RESEARCH HIGHLIGHTS

breakthrough exacerbations, the ‘up’ state were not. marrow microenvironment despite being on standard These results indicate that mediated and epigenetically treatment plans. This finding not Purkinje neurons use bistability driven de novo drug resistance, only expands our understanding to selectively engage or disen- can contribute to the persistence of breath-chemistry associated gage with motor outputs. Such of minimal residual disease

TERRY VINE/GETTY IMAGES TERRY with long-term exacerbations in selective attention might lie at in leukaemia which leads to a asthma, but suggests tailoring the heart of our ability to learn relapse. treatment strategies to detected new manoeuvres — an idea the endotypes to improve outcomes. Thirumalai group is investigat- ing experimentally. Molcular differences were seen in the endotypes of asthmatic children. BERNARD/CNRI J. STATE OF POSSIBILITY Neuroscience To find endotypes of child- Vatsala Thirumalai hood asthma, Tavpritesh Sethi, Senior Fellowship ANNIE CAVANAGH and Anurag Agrawal used AI National Centre for Biological Science, Bengaluru Blood cells from bone marrow in a techniques to analyze chemical eLife 2015 case of acute myeloid leukaemia. patterns in breath samples. The study was conducted In a subset of acute myeloid over five years. At the start, Purkinje neurons are nerve leukaemia called acute pro- the children breathed into an cells located in the cerebellum myelocytic leukaemia, Vikram apparatus that condensed the that are involved in generating Purkinje neurons fired impulses at a Mathews and colleagues have water-vapor and metabolites in coordinated movements. constant rate, while in an 'up' state. demonstrated the significance of their breath, a reflection of their Although they have been this mechanism in resistance to lungs and airway chemistry. studied for almost 50 years, not arsenic trioxide which is used to These samples were analyzed much is understood about how treat this condition. by Nuclear Magnetic Reso- these neurons function.Vatsala LEUKAEMIA DISCOVERY The team further showed Cancer, Clinical research nance (NMR) spectroscopy, a Thirumalai and Mohini Sengup- that in this setting, resistance Vikram Mathews technique used to understand ta recorded the intrinsic activity Senior Fellowship is predominantly driven by the the chemical composition of patterns of Purkinje neurons in Christian Medical College, Vellore NF-kB pathway and that this mixtures. larval zebrafish and showed that Frontiers in Immunology 2018 could be reversed by combining The NMR spectra generat- they were bistable, meaning they arsenic trioxide with bortezomib, ed were used to train a ma- can exist in one of two stable a proteasome inhibitor that also chine-learning algorithm, called states. Despite recent advances the inhibits the NF-kB pathway. Random Forest, which evaluates The output of bistable nerve majority of patients treated for The team’s findings have a candidate as asthmatic or not, cells is dictated by the state they acute myeloid leukaemia will further clarified the mechanism and further divided asthma into are in. Sengupta and Thirumalai experience a relapse, which has of arsenic trioxide in acute pro- endotypes. These endotypes found that Purkinje neurons a high mortality rate. myelocytic leukaemia, and have were learnt by the computer fired spikes, or nerve impulses, The majority of research on been translated into an ongoing without expert input and served at roughly a constant rate when acute myeloid leukaemia relapse Phase II clinical trial in relapsed as a snapshot of airway chemis- they were in the ‘up’ state, in- has focused on somatic muta- acute promyelocytic leukaemia. try at enrollment time. stead firing spikes in bursts when tions leading to clonal evolution, While the breath-NMR they were in the ‘down’ state. and on the concept of a leukae- endotypes of asthmatic chil- The team established the mia stem cell population that is dren were clinically similar by functional relevance of the inherently resistant to conven- conventional measures, they neurons’ bistability by noting tional chemotherapy agents. had molecular differences and that the bursts in the down state However, it is increasing- were associated with markedly were strongly correlated with ly recognized that additional different five-year incidence of motor output but the spikes in mechanisms, such as bone

20 INDIA ALLIANCE K. Srinath Reddy

NAVIGATING THE ROAD TO 2030 DEVELOPMENT GOALS

By 2030, the United Nations’ services. Given this broad agen- THE PACE OF increase of emergency transport deadline for accomplishing da, where is India’s health as it INDIA'S services. Quality of care at the the Sustainable Development sets out on the road to SDGs? TRANSITION institutional level remains a Goals (SDGs), India will have India is undergoing multiple VARIES concern, but if that can be im- the world’s largest population, transitions: developmental, ACROSS A VAST proved, India should be able to having attained that status by demographic, nutritional, LANDSCAPE achieve the 2030 MMR target of 2024. The probability of SDGs environmental, technological AND DIVERSE 70, and the under-five mortal- being reached, therefore, relies and cultural. The pace of these POPULATION. ity target of 25 (down from 43 substantially on India overcom- transitions varies across a vast presently). Neonatal mortality ing its health challenges. If the geography and diverse popula- has remained a major concern, anticipated demographic divi- tion. Aggregate national indi- demanding improvements in dend of accelerated economic cators mask the large variations both antenatal and institutional growth, propelled by a produc- across states and the huge gaps care of mother and baby. The tive population is to be realised, that exist between population National Family Health Survey the country must improve the groups. Still, the rise of NCDs of 2016 has revealed a high health status of its large, and and reduction in the burden of prevalence of undernutrition mostly young population. infectious diseases is a consist- in children under five (38.4% India entered the SDG era ent pattern across the country. stunted; 35.7% underweight; lagging in the health targets set Life expectancy is the second 21% wasted). by the Millennium Develop- lowest in South Asia and mater- Tuberculosis (TB) preva- ment Goals (MDGs). Even as nal and child mortality rates are lence and mortality have been it rededicates itself to improve- four to five times higher than in reduced, but drug resistant TB ments in maternal and child China and Sri Lanka. is rising, with India expected to health, and control of major Maternal mortality ratio have 42% of the world's cases by infectious diseases (TB, HIV- (MMR) is now 130 per 100,000 2020. HIV prevalence has been AIDS, malaria), it must also live births, a vast improvement reduced, but cuts in programme deal with the mounting menace from 677 in 1980 and 556 in funding is increases risk of of non-communicable diseases 1990. The launch of the National resurgence. Malaria continues (NCDs), mental health prob- Rural Health Mission (NRHM) to be a major challenge in states lems, pollutants, and addictions, in 2005 helped achieve the with large tribal populations all now recognised major public decline, with a strong focus and north eastern states. Other health threats. There are also on maternal and child health. vector borne diseases like Chi- further conditions to the global The success came through the kungunya and dengue are now health agenda, with the SDGs induction of women community familiar threats in many parts of also calling for Universal Health health mobilisers in villages, India. There are new concerns Coverage (UHC) and improved financial incentives to promote about the impact of climate access to reproductive health institutional deliveries and the change on health and nutrition.

INDIA ALLIANCE 21 10TH ANNIVERSARY LYNN JOHNSON/NATIONAL GEOGRAPHIC JOHNSON/NATIONAL LYNN

NCDs are now the leading most commonly. Air pollution CHILD demands of prevention, diag- contributors to mortality (63%) takes its toll, both outdoors, MORTALITY nosis and treatment. Access to and loss of Disability Adjusted and indoors, due to burning of RATES ARE quality health care is limited in Life Years (55%). Cardiovascu- solid biomass fuels for cooking. FOUR TO FIVE rural areas and urban slums. lar diseases, cancers, chronic Tobacco and air pollution each TIMES HIGHER With low levels of health obstructive diseases are claiming account for more than a million THAN IN CHINA expenditure overall (1.2% of lives in productive years (56% deaths annually. OR SRI LANKA. GDP) and especially of public of NCD deaths occur below A pronounced predilection financing (25% of all health 70 years; 40% below 65 years). for diabetes contributes to high spending), there are high out- Mental health disorders are a burdens of cardiovascular and of-pocket costs (64%). Private major contributor to morbidity. renal disease, linked to many health insurance has low pene- Even as risk factors like high factors ranging from intra uter- tration. While several govern- blood pressure and cholesterol ine and early childhood malnu- ment funded health insurance and excessive weight are on the trition to diets rich in refined schemes have increased access rise in both urban and rural carbohydrates and sedentary of poor families to hospital populations, undernutrition and lifestyles. High levels of abdomi- care, they have failed to provide air pollution are the top two - nal obesity and low muscle mass financial protection as measured risk factors of ill health in India. portray the physical picture of by out of pocket expenditure, or Tobacco consumption, another metabolic compromise. healthcare related impoverish- major risk factor, has declined While multiple public health ment. It has been estimated that over the past decade, but re- challenges threaten individuals, 7% of the Indian population is mains high with 25% of adults under-resourced health systems pushed into poverty by health using, beedi and cigarettes are overwhelmed by mounting expenditure in any year.

22 INDIA ALLIANCE 10TH ANNIVERSARY

Since 2005, policies to Biomedical, epidemiological, AS INDIA are many interesting scientific strengthen the health system clinical, health systems, health MARCHES questions on gene-environmen- and improve health outcomes technologies, health policy and TOWARDS tal interactions and modifiable have been tried. The National implementation must all be THE SDG 2030 epigenetic effects, as well as the Health Mission (with rural and considered in tandem in order DEADLINE, THE microbiome, that are best an- urban components), the govern- to improve knowledge and have WORLD WILL BE swered in the Indian population. ment funded health financing it translated to useful products WATCHING. Similarly, the role of inno- schemes for the poor (Rashtriya and services. vative, frugal and impactful Swasthya Bima Yojana, soon to Health research must engage technologies in enhancing the be replaced by a larger funded in answering questions that outreach, effectiveness and equi- National Health Protection range from from aetiology and ty dimensions of health services Scheme) and a large number mechanistic pathways to innova- may be studied in the Indian of disease control programmes tive technologies, cost-effective context, but will yield valuable are responding to existing and and affordable delivery systems knowledge which can be applied emerging public health chal- for health interventions, as well in many other countries. As lenges. as the social and environmental India marches towards the SDG Trans-disciplinary research determinants of health. 2030 deadline, the world will be in several domains of health Why do Indians have a pro- watching, to track her progress, must invigorate the mul- clivity for developing diabetes, and benefit from her experience ti-sectoral and health system especially when a third of those and expertise. responses needed for protecting who do are thin? Given the and promoting India’s health. ethnic, genetic, geographic, cli- K. Srinath Reddy is President, Public Research must extend across matic and dietary and develop- Health Foundation of India. Views ex- and integrate several domains. mental diversity of India, there pressed in this article are personal. SANJIT DAS/PANOS SANJIT

INDIA ALLIANCE 23 10TH ANNIVERSARY

24 INDIA ALLIANCE 10TH ANNIVERSARY

THE SEARCH FOR HEALTH SOLUTIONS MUST BE BROADENED NAUFAL MQ/GETTY IMAGES NAUFAL

INDIA ALLIANCE 25 Yogeshwar V. Kalkonde, Devaki Nambiar, Prashanth Nuggehalli Srinivas, and K.M. Venkat Narayan

Human health has improved but substantially increased cost WE NEED A diverse health needs, but where dramatically over the last centu- and side effects with the cost of STRATEGIC researchers face substantial pres- ry: life expectancy has doubled, cancer drugs a very significant VISION THAT sure from powerful stakeholders childhood and maternal mor- variable. UTILIZES like external donors and private tality have fallen, and common The use of expensive ther- CURIOSITY for-profit interests. communicable diseases are apies with marginal benefits AND NEED. Twenty-first century health in decline. Science has played for their approved indications and human development an instrumental role in these and for unproven indications requires greater emphasis on improvements. is contributing to the rising need-driven science. We need However, glaring gaps exist cost of cancer care. We believe a strategic vision that utilizes in our current approach to that expensive therapies are curiosity and need as part of a address the extant human health stifling progress. The prom- whole, guided by basic prin- challenges, and our prepared- ises of genomics, proteomics, ciples that unify science with ness to face emerging issues in and metabolomics — despite health and human development. the global interconnected world enormous investments — are We can use robust surveil- of the twenty-first century. largely still unfulfilled. Further lance systems to systematically Major challenges exist in large gains in life expectancy map health priorities at global, the realm of human health. seem unlikely, necessitating an national and sub-national levels. Recent macro-level data on emphasis on quality of life and Two good examples are the human health and development human development. How can Global Burden of Disease (GBD) have unveiled large disparities science address these seemingly study and the Nutrition Dash- between and within countries. formidable challenges? board Project. These data need Many low- and middle-income We argue that in order to to be made widely available, and countries (LMICs) still struggle address these challenges, science accessible to policymakers. with high rates of poverty, un- will need to undergo a para- Researchers need to address dernutrition and communicable digm shift. Researchers must issues that are high health diseases. aim to expeditiously improve burden priorities. For example, Many new and complex human health worldwide. The hypertension is a leading risk issues affect human health. scientific community needs to factor for death and kills more Threats to the environment, step beyond basic biomedical than 9 million people annually water shortages, anti-microbial sciences and holistically address worldwide. Controlling it can resistance, ageing of popu- behavioural, social, economic, save more lives than any other lations, growing burdens of environmental, and policy con- clinical intervention. Tools to chronic non-communicable dis- texts to improve health. diagnose hypertension are easily eases (NCDs), such as diabetes, There are two prevalent ap- available and multiple inexpen- cardiovascular diseases, cancers, proaches to scientific advance- sive medications exist to treat it. and mental health disorders, all ment: curiosity-driven ­— im- Yet hypertension detection rates have a profound impact on glob- pelled primarily by intellectual remain low and among those al human health. curiosity ­— and need-driven, with diagnosed hypertension in Investments in biomedical guided by objectively measured both lower- and higher-income science seem to have dimin- and perceived needs in com- Yogeshwar V. Kalkonde Society for countries, fewer than half have Education, Action and Research in ishing returns. For example, 71 munities. The tension between Community Health, Gadchiroli, India reasonable control of their blood new cancer drugs were ap- them is particularly relevant in Devaki Nambiar The George Institute for pressure. Global Health, New Delhi, India proved between 2001 and 2012. low- and middle-income coun- Prashanth Nuggehalli Srinivas Institute Focusing on healthcare sys- They improved overall patient tries(LMICs), which have scarce of Public Health, Bengaluru, India tems and delivery can address K.M. Venkat Narayan Emory University, survival by just 2.1 months, resources for science and large, Atlanta, USA such challenges. We also need to

26 INDIA ALLIANCE 10TH ANNIVERSARY

pay more attention to structural ples in India where involving EQUITY AND questions will emerge as new and macro-economic drivers community health workers and ETHICS NEED TO and powerful technologies of common health issues, such implementing participatory BE WEIGHTED evolve to achieve solutions as powerful industrial interests learning and action have led to MORE HEAVILY once considered unachievable. driving environmental degrada- substantial reductions in infant AMONG Many of these will force shifts tion, unplanned urban sprawl, mortality. SUCCESS in social and cultural norms tobacco, processed and sug- Researchers need to work METRICS. and legal structures. We will ar-laden foods. closely with policymakers need continuous conversation Many of the human health and implementers to translate between scientists and society as problems that we face are research findings to improve an integral part of using science exceedingly complex. We need health services. Implementing for human development. collaborative multidisciplinary public health policies based on We are in one of the most approaches to solve them. A re- scientific evidence can bring big exciting eras in human histo- cent example is the development rewards. For example, the use of ry. In the last century, science of a rotavirus vaccine. Rotavirus palm oil — a cheap option for and technology have brought causes between 75,000-122,000 cooking — leads to increased unprecedented health gains. deaths each year in India. A serum cholesterol levels. When Most of those gains have origi- team effort — involving clini- the government of Mauritius nated in areas of science outside cians, virologists, epidemiolo- initiated a programme to switch biomedicine, and this is likely gists, a biotech company and a people from palm oil to soya to be even more frequent in the publicly funded governmental bean oil, serum cholesterol coming century. To improve organisation, universities, and levels were significantly reduced human health, we will have to a philanthropic organisation in the community. pay great attention to popula- from India and the United Equity and ethics need to be tion needs and direct scientific States — led to the successful weighted more heavily among research from a core vision of development of an effective and success metrics to guide science human development. inexpensive vaccine. for health and human develop- Strong and independent Health researchers need to ment, particularly when consid- national institutions, similar to view communities not as passive ering disadvantaged populations the US National Academies of recipients of their work, but who often do not have a voice in Science, Engineering, and Med- as engaged co-creators. There determining research priorities. icine, can help keep the vision are several successful exam- Also, profound ethical and focus on human develop- ment. We urgently require more funding for need-driven science aimed at human health, and to integrate basic and population TIM GAINEY/ALAMY TIM health sciences towards this end. The Wellcome Trust/DBT India Alliance is an example of such efforts. Good health and well-being is crucial for human development, as articulated in the United Nations’ Sustainable Development Goals. Realiz- ing that aspiration will need in ample measure the wisdom of Goethe: “Knowing is not enough, we must apply. Willing is not enough, we must do.”

INDIA ALLIANCE 27 10TH ANNIVERSARY GIACOMO PIROZZI/PANOS GIACOMO

28 INDIA ALLIANCE Shweta Khandelwal, Giridhara R Babu, and Anura V Kurpad

WEIGHING THE PARADOX OF UNDERNUTRITION AND FAT

The decline of India’s rate of subsidized cereal grain for poor OBESITY IN Political will, ownership and undernutrition is stubbornly and vulnerable segments of the INDIA HAS BEEN decentralization are critically slow, while numbers of people population. FUELLED BY important for ensuring nutrition who are overweight and obese However there has been a THE LOW COST through the life course. are soaring. Its population is systemic failure of implemen- OF SIMPLE It can be difficult to turn transitioning from one group tation. For example, there has SUGARS AND science into policy. Evidence to the other alarmingly quickly, been a more than threefold UNHEALTHY generation has come to demand with few in a state of optimal increase in food grain procure- FATS. the rigour of a randomized nutrition. ment by the government during controlled trial. However, the Too many of its young the past two to three decades, randomized controlled trial population suffer from chronic yet inefficiencies in storage and design does not lend itself easily diseases that would not be ex- distribution has resulted in the to the multiplicity of nutrients pected until middle age in other inadequate supply of grains to in food or the complexities of parts of the world. Only one in those in need, leading to the food production, access, and ten children between six and 23 extraordinary paradox of rotting consumption. Frameworks months of age has an ‘adequate of food grains amidst wide- that reduce foods to nutrients, diet.’ One in three preschool spread hunger. offer one way to overcome this children are malnourished and Substantial scope remains problem. But, they might also the proportion of urban over- for implementation and advoca- oversimplify complex pro- weight children is increasing. cy research in nutrition, focus- cesses and eventually, form a The nutrition imbalance has ing on the complex operational distraction to the necessity of knock-on effects for the envi- problems arising from efforts to providing diverse and whole ronment, and for the economy, alleviate poverty and malnu- foods. This approach has led to and wealth generation. For trition. Sound research should several single nutrient policies, example, the swift increase in inform successful policies, but such as food fortification, where obesity rates in India has been good governance and coordi- the intake of a single nutrient is fuelled by the low cost of simple nation is needed to put those pushed, without any behavioural sugars and unhealthy fats, policies into action. change in the population. while healthy foods like fruits For example, the provision India’s policy on anaemia and vegetables are not readily of subsidized nutritional food has focused on iron, and there accessible. India has imple- might appear to be a clear and is nothing immediately wrong mented almost every possible simple task, but the responsibili- with that. However, when this policy to improve the state of ty for it is fragmented. Child de- has failed, the answer lies in nutrition and alleviate poverty. velopment, maternal and child better implementation, or in These range from micronutri- health, and education are locat- innovative approaches that ent supplementation and the ed in different ministries, which improve dietary iron absorption. provision of cooked food, to do not always work together. Simply increasing the delivery of

INDIA ALLIANCE 29 10TH ANNIVERSARY

dietary iron, also risks exceeding the limit of beneficial intake. In contrast, perhaps the best example of a holistic approach is the lesson from the adoption of very stunted Indian children ADOBE/THEFINALMIRACLE into Sweden. The height-for- age ratio of these children was improved by more than two standard deviation scores in the two years after their adoption. This was not the result of any single intervention, but from a general attention to health, a clean environment, diverse foods, and perhaps a great deal of love and attention. In contrast, the rate of reduction in the prevalence of stunting is moving at the glacial annual pace of 1.3% in India, compared to much faster progress in neighbouring countries. Research encom- SOUND health. Yet researchers across evidence-based policies, guided passing multiple health factors, RESEARCH disciplines do not communicate by India’s operational priorities. including affordability, availabil- SHOULD INFORM effectively. This is now happening with the ity and access to food, the ability POLICIES, BUT GOOD Research that has defined establishment of the National to maintain healthy behaviours, GOVERNANCE IS the nutritional demand or Technical Board on Nutrition at and enabling circumstances, is NEEDED TO PUT bioavailability of nutrients the Niti Aayog, and bodes well important. THOSE POLICIES from different foods does not for the nation. Another factor in India’s INTO ACTION. inform agricultural policy. Food Policymakers must use poor public health and nutri- production, procurement, dis- research to inform their tion, and sub-optimal research tribution, and subsidy in India decision-making. Funding outputs, is the lack of sustained are still cereal-centric, when support must be used to drive mentorship, capacity building there is no good nutritional researchers to focus on provid- and strengthening initiatives. reason to remain this way. ing solutions. Robust research The lack of a comprehensive Recently, an online dashboard that informs national schemes understanding of this multidi- has been made available, which and programmes, along with mensional problem, coupled describes Indian food produc- effective advocacy and favoura- with inadequate attention to tion, consumption, nutrient ble economic policies, will help nutrition education and research intake and health. It is hoped alleviate the country’s nutrition- skills, undermines the country’s that research approaches that al deficiencies. ability to reach the goals of the include the triangulation of 2017-2020 National Nutrition national datasets and geospatial Shweta Khandelwal, Public Health Foun- Strategy. modelling will inform strate- dation of India, Delhi NCR, India. There is great potential gic research agendas and food Giridhara R Babu, Intermediate Fellow, India Alliance; and Additional Professor, for finding solutions between policy. A network of research- Public Health Foundation of India.Cor- sectors, including agriculture, ers, policymakers and other responding Author: Anura Kurpad, St John’s Medical College, Bengaluru, India. economics, nutrition and stakeholders should formulate [email protected]

30 INDIA ALLIANCE Guruprasad R. Medigeshi and Gagandeep Kang

VACCINES ARE VERSATILE, VALUABLE AND VITAL

More than 1,000 years ago peo- century, resulting in the World MOST the world, because a good vac- ple in India and China protected Health Organization’s estimate VACCINES cine was used effectively. Polio themselves from smallpox with that vaccines save 2.5 million MADE IN INDIA was identified as the next target, one of the earliest known prac- lives every year. In the 1960s and ARE HIGH and the world is on the verge of tices of inoculation by rubbing 1970s, Maurice Hilleman, a vac- VOLUME AND becoming free of polio ­— again the powdered scab from an cinologist, developed more than LOW COST, a goal being achieved through infected patient into a cut in the 40 vaccines and is credited with BASED ON prevention of infection. skin of a healthy person. This saving more lives than any other TECHNOLOGIES However, not all diseases gave protection from disease in medical scientist in history. DEVELOPED are amenable to easy vaccine some people, but it also spread Most vaccines are made ELSEWHERE. development. Viral targets have the disease in others, sometimes using traditional means of been simpler than bacteria, and fatally. weakening or killing the whole diseases such as malaria, den- The story of Edward Jenner, organism, (attenuated or dead gue, tuberculosis and AIDS are who observed the smooth skin vaccines) and technological likely to remain a major vaccine of milkmaids and translated that advances have ensured mass hurdle for many years. Most knowledge into using cowpox to production and supply across existing vaccines were created protect against smallpox, is well the world. using traditional approaches, known, and it is this discovery Measles vaccines alone have however, as we enter the phase that laid the foundations for the prevented an estimated 20.4 of developing vaccines for creation of modern vaccines. million deaths from 2000 to complex pathogens/diseases — Until the 20th century, no- 2016. Vaccines are undoubtedly such as dengue virus, different one recognised that cowpox and the most cost-effective solution influenza virus strains, tuber- smallpox were caused by virus- to prevent diseases and provide culosis, and AIDS — there is a es, or that inducing protection the best returns on investment need to adopt novel and smart against one resulted in protec- in public health, protecting not approaches. tion from the other, a phenome- just those who receive them, but The development of vac- non known as cross-reactivity or curtailing infection rates with cines is a long and hard road, cross-protection. community uptake. This phe-� requiring many years and stages But, while the effectiveness nomenon, known as herd im-� of assessment; first in animals and safety of vaccines is proven munity or herd protection, may (pre-clinical toxicity), then in beyond doubt, new challenges eventually help eradicate many humans (phase 1), the ability have emerged, from falling previously dreaded pathogens. to induce an immune response vaccination rates in developing (phase 2) and for protection countries, to the anti-vaccine CHALLENGES IN MAKING from disease (phase 3), as well movement in the West. VACCINES as standardization of the man- The production and use of Smallpox was the first human ufacturing process for complex vaccines came of age in the 20th disease to be eradicated from biological material.

INDIA ALLIANCE 31 10TH ANNIVERSARY ARINDAM DEY/AFP/GETTY IMAGES DEY/AFP/GETTY ARINDAM

Challenges in vaccines come has suffered serious setbacks, WHEN Furthermore, a wide gap in from the complexity of the or- with some of the most prom- DISEASES resources, geopolitical stability ganism or the complexity of the ising candidates failing at late DISAPPEAR, and population distribution has response to the vaccine. Almost stages of testing. However, failed PEOPLE BECOME resulted in disproportionate 100 years since the develop- attempts have provided insights COMPLACENT vaccine coverage rates across ment of the Bacille Calmette- into human immune response ABOUT VACCINES the world. In addition, coverage Guérin (BCG) vaccine, we have to HIV, which have propelled OR DISCOUNT rates vary for different vaccines. not been successful in either efforts towards better strategies THEIR VALUE. Global vaccine coverage has combating tuberculosis (TB) and partnerships. Similarly, remained stagnant at 86% for or developing a vaccine that studies using controlled human the vaccines covered under the is more effective than BCG. infection models are providing universal immunization pro- Nevertheless, more than a dozen evidence for a better malaria grams, and vaccine coverage for potential vaccine candidates and dengue vaccines. For new some of the newly introduced for TB are at different phases of and effective vaccines, new vaccines, such as rotavirus is evaluation. partnerships are needed, involv- barely 25%. The Global Vaccine There is an urgent need to ing disease biologists, vaccine Action Plan (GVAP) had set supplement these vaccine de- developers, epidemiologists and lofty goals of equitable access to velopment efforts with relevant clinician researchers. vaccines by 2020, but only one and reliable information on Despite best efforts of vari- of the goals is on track. 73% of biomarkers of disease or those ous countries and multi-lateral the world’s poorest people are in that predict protection. agencies, one in 10 infants did low-and middle-income coun- AIDS vaccine development not receive any vaccines in 2016. tries (LMICs) and delivering

32 INDIA ALLIANCE 10TH ANNIVERSARY

vaccines to these resource-poor panies, which produce millions settings must be a global pri- of doses of vaccines every day, ority. The establishment and supply the global south with this sustenance of the Gavi Alliance essential tool for prevention. has been a game-changer over Vaccines are vital for pre- the past 15 years, supporting vention of disease and have been LMICs to introduce new vac- a success story. India’s contri-

cines and improve their immu- bution to public health vaccines IMAGES SAFODIEN/AFP/GETTY MUJAHID nization programs. The logistics has been enormous, however, of getting vaccines to certain most vaccines made in India countries and keeping them are high-volume and low cost, in appropriate storage is also a based on technologies that were challenge. For example, because developed elsewhere. vaccines need to be kept cold, a In order to make new and purpose-built cold chain points innovative vaccines and to distribution system needed to be vaccine, untrue and disproved. Close to 60 countries are en- use them, we need a focused created in India. These messages can significantly demic for yellow fever, with an investment in research and Vaccines avert disease and impact vaccine coverage rates, estimated at-risk population of development, with partnerships death, but when diseases dis- and, as in the cases of measles, one billion. Yellow fever vaccine between academia, industry and appear, people become com-� cause outbreaks through unvac- was the first successful vaccine government, backed by a sci- placent or discount the value of cinated and vulnerable children. developed against a human vi- entifically educated population vaccines. Anti-vaccine lobbyists Despite vaccines being de- rus, in 1938, however the supply which recognizes the value and count on respite from the dis- veloped and available for several of vaccine has not kept pace benefits of prevention. ease to highlight fears about the decades, many people at risk do with the disease. This is because side-effects of vaccines­ — some not get them. Brazil is dealing vaccines, as public health inter- Guruprasad R. Medigeshi and Gagan- real but rare —­ and others, such with more than 1,000 cases of ventions, need to be cheap and deep Kang, Translational Health Science as the autism link to the MMR yellow fever. affordable. India’s vaccine com- and Technology Institute, Faridabad, India.

Panniyammakal Jeemon, Elezebeth Mathews, and Vivekanand Jha

A MODERN CONDITION? TAKING ON NON-COMMUNICABLE DISEASES

For most of history, threats to more significant. Dumped under ascribed to four common and attributable to NCDs, and they, healthy life have come from an umbrella term of non-com- modifiable behavioural risk along with injury, constitute pestilence, famine, injury and municable diseases (NCDs), factors: tobacco use, alcohol seven out of the top 10 causes complications of childbirth. As these conditions are character- consumption, unhealthy diet of death and nine of the top 10 humans conquered these con- ised by chronic illness, multi- and lack of physical activity. causes of disability. ditions and lifespans increased, morbidity, unequal distribution NCDs are the leading causes of Most NCD-related deaths in new problems like diabetes, that disadvantages the poor and death and disability in India: India are premature — over 52% hypertension, cardiovascular, the vulnerable, and lack of prop- nearly 62% of all deaths and of cardiovascular deaths occur respiratory, and kidney diseases, er health system response. 55% of all disability-adjusted below the age of 70, while it is and mental health issues became Most of the NCD burden is life years (DALYs) in 2016 were 23% in high-income countries.

INDIA ALLIANCE 33 10TH ANNIVERSARY

The myth that NCDs were hospitalisation for cancer and Communicable facts seen mainly in urban popula- cardiovascular disease in India Myth Fact tions was destroyed as early as were respectively 160% and 30% Call for investments NCDs are the leading cause of death and disability 2003, when NCD mortality in greater than when the hospital- in NCDs in India is in India. Three out of five deaths in India are due to premature NCDs. NCDs are a health concern for most of the rural India (41%) was shown isation was for a communicable Indian population. to be almost the same as that disease. OOPE attributable to NCDs are primarily urban Even in 2003, NCD mortality in rural India (41%) was due to communicable diseas- NCDs rose from 32% in 1995-96 diseases almost the same as that due to infection (40%) and had risen to 47% by 2010-13. Several surveys have es, maternal and perinatal con- to 47% in 2004 [6]. It is estimat- shown similar NCD risk-factor prevalence in urban ditions and nutritional disorders ed that NCDs reduce the gross and rural areas. (40%). The figure rose to 47% domestic product of India by at NCDs are disease of NCDs burden is increasing at a greater rate amongst the rich the poor in India. NCDs develop earlier in life by 2010-13. Between 1990 and least 1%. amongst the poor and the marginalized.

2016, the all-age death rate NCDs are disease of the A majority of deaths due to NCDs in India are increased by 131% for diabe- WHY ARE NCDS elderly premature and preventable. Additionally, years of productive life lost due to NCDs are greater than tes, 55% for ischaemic heart INCREASING? those due to communicable diseases. disease and 33% for chronic Increasing life expectancy, grow- NCDs are primarily NCDs affect women equally to men and more in the kidney disease. DALY rates also ing population, urbanisation diseases of men. post-menopausal age group. The effects of some risk factors like smoking and diabetes on CVD risk increased for diabetes, ischae- and changing lifestyle are the are disproportionally stronger in women. mic heart disease, sense organ major drivers of the rising NCD Increase in NCDs repre- The global cost of NCDs in the coming two decade disorders, lower back and neck burden. With the rise in diabe- sent economic growth is estimated at around US$30 trillion. India will have lost US$4.58 trillion due to NCDs by 2030. pain, migraine, chronic kidney tes, hypertension and obesity, NCDs are incurable Most NCDs are incurable, but premature deaths disease, depressive disorders, population ageing and climate and disability due to NCDs are preventable using and anxiety disorders. change, NCD-related deaths evidence-based interventions. The heterogeneity of India is and disability are expected to NCDs are self-inflicted Initiating societal change for behavioural modifica- and the state has no role tion and providing incentives to make good health reflected in the communicable rise further. The pace of change in prevention choices are the responsibility of the state. Smart disease-to-NCD transition. The combined with a vast population urban planning, affordable and accessible healthy foods, quality health education and limitations on date when the number of NCD make the problem particularly the advertising of unhealthy products are strategies DALYs first exceeded DALYs acute for India. to reduce NCDs. Behavioural risk factors Good quality evidence suggest that lifestyle inter- due to CMNNDs ranges from The traditional risk factors for NCDs are difficult to ventions are useful in delaying the onset of diabetes 1986 to 2010 in different states. around which the current health change and are scalable. In the early transition states, interventions are structured ac- Lifestyle changes are Initiating healthy lifestyle changes early in life helps for people who have delay the onset of diabetes, hypertension and other 67% of all DALYs in 2016 were count for only half of the NCD diabetes, hypertension, NCDs. attributed to NCDs, whereas burden in India, suggesting that and heart attacks. the figure was 49% for late additional reasons remain to be People are very busy. Physical activity is the magic bullet to prevent NCDs. Physical activity takes It only takes 30 minutes of moderate-intensity transition states. The transition discovered. Unique risk factors too much time. physical activity five days per week to improve and is directly related to the level that might contribute to the maintain your health. of social development, with NCD burden include a propen- NCDs have no relevance Smoking and alcohol use are high among today’s to young people youth. They will drive the future NCD epidemic. more developed states having sity for metabolic syndrome at Targeting them early is therefore a good option. greater NCD burden. The poorer a lower body mass index, high states are catching up, however. rates of intrauterine malnutri- liver disease, H. pylori for peptic during adolescence, pregnancy NCD DALYs increased by 65% tion followed by exposure to cal- ulcer disease and gastric cancer and lactation. between 1990 and 2016 in late orie-rich food later in life, wide and (as yet unidentified) envi- transition states, compared to availability of diverse tobacco ronmental causes for chronic THE INDIAN RESPONSE TO 36% in early transition states. products, indoor air pollution, kidney disease and cancers. The DISEASE The economic consequences and environmental toxins. Some role of the microbiome in the Until recently, the Indian health- of NCDs cannot be overstated. risk factors (including infec- genesis of NCDs is in the early care system laid emphasis on NCDs push large numbers of tions) are unique to specific stages of exploration. Concerns sanitation, infection control and people into poverty. The poten- NCDs, for example, human pap- related to trans-generational care of the mother and child tial for incurring out-of-pocket illomavirus infection for cervical transmission of NCDs have led during and after pregnancy. expenditure (OOPE) during cancer, hepatitis C for chronic to consideration of interventions Several system-level barriers

34 INDIA ALLIANCE 10TH ANNIVERSARY JAKUB SLIWA/AURORA PHOTOS SLIWA/AURORA JAKUB

have prevented appropriate NCD prevention and control. As INDIA IS A India was the one of the first responses to NCDs: a lack of a result, NCD care slipped into FREQUENT countries to develop targets in risk-factor and disease surveil- the domain of the profit-driven DESTINATION response to the World Health lance systems, poor access to private healthcare industry. FOR MEDICAL Organization’s global action plan drugs and diagnostic services, High-end tertiary care hospitals TOURISTS for the prevention and control of limited public financing or provide cutting-edge curative SEEKING CARE NCDs for 2013-2020, aimed at insurance, and human resource medical care for NCDs to those FOR A VARIETY reducing the number of global limitations. Although India has who can afford it. Indeed, India OF CHRONIC premature deaths from NCDs by been the largest recipient of is a frequent destination for CONDITIONS. 25% by 2025. The Union Gov- overseas development assistance medical tourists seeking care for ernment launched the National for health, little of it has been for a variety of chronic conditions. Program for Prevention and

INDIA ALLIANCE 35 10TH ANNIVERSARY

Control of Cancer, Diabetes, of an integrated NCD policy THE PACE OF guided by an assessment of com- CVD and Stroke (NPCDCS) in India. effectively Combat- CHANGE munity health, consider broad in 2010 with the aim of health ting NCDs requires reforms at COMBINED health determinants, address all promotion through behaviour multiple levels, starting from WITH A VAST levels of prevention and practice change, outreach camps for legislative action, such as im- POPULATION and are appropriate for delivery opportunistic screening, setting posing taxes on unhealthy food, MAKE THE in the community need to be up of NCD clinics, capacity tobacco products and alcohol; NCD PROBLEM evaluated. Suggested approaches building, and providing support enforcing mandatory labelling PARTICULARY include task-sharing, in which for the diagnosis and cost-effec- on packaged foods; developing ACUTE FOR frontline health workers provide tive treatment of NCDs. infrastructure to facilitate good INDIA. standardised care using simple The operational guidelines, lifestyle choices — providing checklists, use of evidence-based however, have undergone sever- bicycle paths, making roads safe decision-support tools based al changes and are still evolving. for cyclists, public spaces for on standardised evidence-based Currently, NCDs are managed sports, and providing healthy algorithms/pathways and use of in the community by multiple food choices in schools. These fixed-dose combinations. stakeholders. Low detection should be supplemented with Such interventions can rates, high rates of treatment awareness campaigns through be implemented by the use of attrition, non-compliance and mass media and social media; mobile technology, wireless net- uncontrolled disease status are ensuring adequate numbers works and point of care devices. important concerns for NCD of clinical personnel, facilities We need to develop capacity control and management. and basic drug supply chains; for secure transmission, storage More recently, the NITI and efficient referral pathways. and analysis of electronic data. Aayog (National Institution Non-government organisations Research is needed to identify for Transforming India) has and the private sector can con- how health programmes can been tasked with implementing tribute to these efforts. Socially reach disadvantaged groups and programs in response to the and economically vulnerable reduce disparities. Multidiscipli- United Nations Sustainable De- groups require more attention. nary collaboration involving al- velopment Goals Agenda, which Insurance and finance reforms lied sectors such as agriculture, includes the target of reducing that align incentives with quality urban planning, environment, preventable NCD deaths by a and outcomes are essential to education, finance, trade, invest- third by 2030. The Ayushman maximize return on investment. ment and transport is needed Bharat Yojana, or National to develop a comprehensive re- Health Protection Scheme, aims SETTING AN EFFECTIVE sponse to the current and future to create health and wellness RESEARCH AGENDA healthcare challenges. Funding centres to provide primary Development of a proper NCD bodies should prioritise a com- healthcare and provide insur- policy response that converts prehensive health system-fo- ance coverage of up to ₹500,000 the current ‘cure-based reactive cused NCD research agenda (~US$8000) to a family per year. model’ into a ‘care-based proac- including capacity building. The scheme currently covers tive healthcare model’ requires The Wellcome Trust/DBT India in-hospital secondary and more research. We need gran- Alliance Clinical and Public tertiary care, but mechanisms to ular data — disaggregated on Health Fellowship Programme is pay for the chronic outpatient the basis of geography, gender, helping the development of such care and medication costs, the caste, religion, occupation and researchers and analysts. major drivers of NCD-related socio-economic gradients — in OOPE remain unclear. order to better understand the Panniyammakal Jeemon Achutha Menon disease drivers and determinants Centre for Health Science Studies, Kerala, WHAT IS NEEDED? of care and to develop targeted India Elezebeth Mathews, Central Uni- versity of Kerala, Kasaragod, India. The WHO NCD Progress Moni- intervention programs. Public Vivekanand Jha The George Institute for tor 2017 has highlighted the lack health interventions that are Global Health, India

36 INDIA ALLIANCE 10TH ANNIVERSARY AAMIR AHMED, JANE PENDJIKY AND MICHAEL MILLAR PENDJIKY JANE AAMIR AHMED,

INDIA ALLIANCE 37 Pritha Paul, Nikhil Patkar, Vikram Mathews, and Vaskar Saha

TRANSLATIONAL CANCER RESEARCH IN INDIA

Despite a global increase in the is set to widen as therapies are CLINICAL that the right questions are incidence of cancer, its mortality not readily accessible and costs SCIENTISTS asked and that the integrity of rate is falling in high-income prohibitive. India needs a strong ENSURE samples and data are main- countries (HICs), due to early research base which improves THE RIGHT tained. The first investment is in detection and prevention, di- patient outcomes, while ben- QUESTIONS ARE the training of skilled clinicians. agnosis and monitoring, along efitting the economy. The key ASKED. Institutions need to identify the with standardisation of treat- components of translational most able of their clinical train- ment and care. With advances medicine are: skilled clinical ees, provide the right resources gleaned from the cancer genome scientists; systemic management and environment, protected project and its offshoots, man- of patients, best achieved within time for research and clear agement of patients in HICs is clinical trials; standardised bi- career pathways. moving to precision personal- orepositories; dedicated funding Initiatives have been ised therapy. The cancer moon- streams, and the availability launched to improve the quality shot seeks to apply a detailed of high-quality data systems. of care for cancer patients. The ‘omics approach using small Development of such networks National Cancer Grid (NCG), molecules and immune-based require collaboration between established in 2012, and therapies to target biological multidisciplinary teams of clini- supported by the Tata Trust, processes unique to cancer cians and scientists, supported has begun developing uniform cell survival. The ambition is a by private-public partnerships. standards of care across 143 result of translational research The increased number of centres and supporting aca- partnerships between academia, patients at tertiary cancer centres demic led clinical trials. New government and industry. are encroaching on protected regulations for academic led Cancer survival rates lag time for research. Even when clinical trials pass the respon- behind in low to middle-in- funding is available, bureaucratic sibility of governance to local come countries (LMICs), such hurdles delay hiring of staff, and ethical boards, but there is much as India. There are multiple purchase of equipment, making it variation in regulation and challenges to the development difficult to complete projects. In- clinical practice. The Clinical of standards of care for patients stitutions lack dedicated research Development Services Agency in India. Cancer treatments at support staff, leaving investigators (CDSA) is implementing prac- Indian centres are mainly based to perform administrative work. tice standards for conducting on protocols developed in HICs, High-quality research cannot be clinical trials across centres and but outcomes are dependent supported entirely from grant a national framework for local on healthcare systems, not just income, and institutions need Nikhil Patkar Tata Memorial Centre, review boards with an active protocols, so management must to invest in infrastructure and Mumbai, India SIDCAR/FERCAP accreditation Vikram Mathews Christian Medical be adapted to local conditions. personnel to successfully develop College Hospital, Vellore, India programme for ethical review. With the move to precision translational research. Pritha Paul, Vaskar Saha There are high-quality The Tata Translational Cancer Research therapy, the gap in survival rates Clinical scientists ensure Centre, Kolkata, India cancer biorepositories at the Tata

38 INDIA ALLIANCE 10TH ANNIVERSARY

Memorial Hospital, Mumbai, the Indian Institute of Technol- ogy, Chennai, the Rajiv Gandhi Cancer Institute, Lucknow, and at the Tata Medical Center, Kolkata. Other institutions have also developed tissue banks. The availability of banked tissue underpins the human genome IMAGES INDRANIL MUKHERJEE/AFP/GETTY project and The Cancer Genome Atlas (TCGA), but raises the problems of a lack of uniformity in sample processing, quality control and reproducibility. Rec- ommendations for standards for ethical collection of tissue, pro- cessing, storage and downstream applications, regularly updated, are available from IARC, NCI such people. Funding pro- MOST CANCER research establishments at major and ISBER and standards for grammes need to be designed to PATIENTS SEEK tertiary cancer centres. We have accreditation processes are support translational research, TREATMENT all benefitted from India Alli- being developed. A national distinct from basic research. WITHIN LARGE ance funding after it quickly saw framework for biorepositories is The primary requirement METROPOLISES. the need for a dedicated funding needed, along with a transparent in India is the development of THE FIRST STEP stream for clinical researchers. process so researchers can inter- standardised care for cancer IS INTEGRATION. Grant review is timely and rogate the archive. patients across tertiary and peer reviewed, though feedback Government science funding secondary care centres, and the in successful and rejected grants is less than 0.9% of India’s GDP, delivery of rapid and cost-ef- could be more explicit. The India and funding for cancer studies fective solutions. The focus is Alliance has taken on board sug- is focused on basic research. to use cheaper therapies, with gestions from its grantees to run Compared to HICs, global repurposing or repositioning workshops, and ensure that re- pharmaceutical and charitable of drugs and to reduce waiting searchers are supported by their investment for clinical research times. This requires collabora- institutions. Though the funding in India is poor. We have all tions across the sectors. Most pool is limited, it is a successful struggled to obtain funding for cancer patients seek treatment blueprint. Through our grants, translational research with grant within large metropolises, and we have instituted national and committees either feeling that the first step is integration international collaborative re- the application was 'too basic' or of centres to remove patient search, established clinical trials 'too clinical'. There is a lack of uncertainty about where they that have established standards transparency on timelines from are likely to get the best care. It of care (Saha, Mathews), devel- a grant call to the award of the makes use of available skills, and oped companion diagnostics at grant, and when awarded fund- spreads the clinical load more point of care (Patkar) and taken ing is often delayed or reduced, evenly. Solutions that work for observations made at the bedside making research planning and Indian patients are likely to have back to the laboratory (Paul). execution difficult. Clinical impact globally. To make this Our experience shows that it is scientists depend on skilled work, requires cooperation from eminently possible to develop and trusted technical staff, but all stakeholders. successful translational cancer uncertain funding undermines All authors of this article research programmes in India. the ability to retain and promote are embedded within dedicated

INDIA ALLIANCE 39 Mriganka Sur, S.P. Arun and Urvakhsh M. Mehta

A NERVE CENTRE FOR NEUROSCIENCE

Since its founding, The Well- neuroscientist, fascinated by I WAS of Mental Health & Neuro- come Trust/DBT India Alliance- how the brain performs object CONCERNED sciences, Bengaluru in 2007. I has been a strong facilitator of recognition. ABOUT received an Early Career Fellow- Indian neuroscience. We have I was concerned about WHETHER I ship from the India Alliance for seen its role up close in different whether I would be able to WOULD BE ABLE studying the neuromodulatory ways. One of us (MS) has served pursue my passion in India, but TO PURSUE MY effects of Transcranial Magnet- on the India Alliance’s fellow- I was fortunate for two develop- PASSION IN ic Stimulation on the mirror ship reviewing committees for ments around that time. First, INDIA. neuron system — an important the past 10 years. Two of us the Centre for Neuroscience was social brain network in schiz- (SPA and U.MM) have received established at the Indian Insti- ophrenia. The fellowship has fellowships from the India tute of Science, an ideal setting enabled me to build advanced Alliance. for interdisciplinary research. skillsets (e.g., neuroimaging From the top down, and I joined here, and continue to analysis and neuronavigational the bottom up, the conclusion work. Second, the newly formed brain stimulation), by providing is clear: the Alliance has been India Alliance had announced the opportunity to train with transformative for the growth its first round of fellowships. I my external sponsors in leading of neuroscience in India. It has started out as an Intermediate institutes worldwide. This has built a critical mass of young Fellow and I am delighted and opened up a broad range of scientists, across diverse insti- honored to continue my associa- translational avenues, as well as tutions, undertaking first-rate tion, now as a Senior Fellow. collaboration prospects. neuroscience research that Over the years I have come The India Alliance has been ranges from molecular and cel- to realize what a high bench- particularly sensitive to the lular, to systems, computational, mark the India Alliance has set challenges faced by Indian cli- and clinical neuroscience. It has for every aspect of science fund- nicians in pursuing high-quality provided these scientists with ing, particularly in the Indian research. They have operated unmatched resources and flexi- context. The fair and thorough closely with host institutions to bility to build a sector that was review process, professional implement innovative working desperately needed in India. handling of all grant-related models that ensure protected matters, generous, flexible fund- research time for their fellows, S.P ARUN I left India as an elec- ing and constructive feedback, without compromising clinical trical engineer from IIT Bombay have enabled India Alliance care. These are worth emulat- in 1999, completed my PhD at Fellows to take their science to ing across the country’s diverse Johns Hopkins, and trained as a the next level. funding systems. postdoctoral fellow at Carnegie Mellon University. By the time U.M MEHTA I trained in psy- M SUR Neuroscience sits at the I was ready to move back to chiatry and started my academic interface of disciplines which India in 2009, I had become a career at the National Institute have traditionally been regarded

40 INDIA ALLIANCE 10TH ANNIVERSARY DR JONATHAN CLARKE DR JONATHAN

INDIA ALLIANCE 41 10TH ANNIVERSARY

separately, such as molecular centives for clinical research and WE BELIEVE IT opportunities for trained PhD biology, physiology, computer sparse research-dedicated infra- MAY BE TIME scientists and engineers. science, and clinical medicine, structure in most institutions FOR INDIA The India Alliance could and often relies on other fields across India, severely limits the TO HAVE ITS consider expanding its pro- to make advances. Neurosci- means and abilities of clinicians OWN BRAIN grammes to include doctoral ence, by definition, has difficulty to contribute to research. INITIATIVE. fellowships in addition to its in gaining a toehold in countries These problems are of course elite postdoctoral (Early Career) or institutions where traditional not limited to the clinical neu- and faculty (Intermediate and departments have high walls. By roscience specialties. The India Senior) fellowships. explicitly promoting cross-dis- Alliance has recognized the We believe it may also be ciplinary life sciences and rec- need and implemented innova- time for India to have its own ognizing high calibre scientists, tive funding schemes that not brain initiative. Such an initi- the Alliance has had a profound only facilitate research training ative should address domestic influence on the growth of Indi- for clinicians, but also provide needs, stand on the twin pillars an neuroscience. protected research time. But of basic and clinical neurosci- In addition to reflecting on more expertise and training in ence, embrace a diversity of the accomplishments of the past research, and investment in re- approaches ranging from indi- 10 years, it is also timely to ask search infrastructure, is needed vidual curiosity-driven research what is needed, and what role to make progress. Clinical neu- to collaborative partnerships the Alliance can play. roscience cannot make headway bridging clinical and basic India represents a fifth of without a solid foundation of neuroscience, have long-term, the world’s population, spread basic neuroscience and neuro- as well as short-term goals, and across an extremely diverse technology. implement a mission of building socio-cultural and geopolitical As the tools of modern neu- the human resources and infra- landscape. It also accounts for roscience have expanded, driven structure for neuroscience. 15% of the global disability recently in large measure by Research is a necessity to burden attributable to brain initiatives elsewhere, India will address fundamental mecha- (neurological, neuropsychiatric, lag further behind unless it can nisms of brain development and substance use) disorders. recruit substantial numbers of and function and its disorders. The magnitude of this burden in talented scientists and engineers While the Indian government India has grown by 61% in the into the field. needs to be the major player in last couple of decades. Though the structural issues an Indian brain initiative, the While the burden of brain are larger than the India Alli- India Alliance — as a convener disorders crosses national ance, certain signs are prom- of top-quality science, and with boundaries, increased emphasis ising. India has a large pool of its decade-long contribution to on clinical neuroscience re- talented students who receive the Indian research landscape search with a vision of bridging undergraduate degrees in sci- — could play a significant role, the translational gap between ence, medicine and engineering. alongside private foundations, fundamental research and its The educational gap between such as the Pratiksha Trust and application to clinical diagnos- the life sciences and the physical Tata Trust, which have invested tics and therapeutics should and engineering sciences, along in impressive basic, clinical and certainly be a priority for India. with the compartmentalization computational neuroscience At least in the near future, of teaching from research, is di- initiatives. however, the drivers of neuro- minishing. As pay scales climb, a Like its counterparts in science research in India are un- career in research becomes more Urvakhsh Mehta National Institute of space sciences or physics, likely to be clinicians. An inad- viable. The number of research Mental Health and Neuro Sciences, Ben- India’s brain initiative will also galuru, India equate doctor-population ratio, and teaching institutions has S P Arun Indian Institute of Science, benefit by forging international the resulting increased clinical grown markedly in recent years, Bengaluru, India collaborations with other brain Mriganka Sur Massachusetts Institute of workload, alongside limited in- providing substantial career Technology, USA initiatives across the world.

42 INDIA ALLIANCE Arun K. Shukla and Shankar Subramaniam

THE CHALLENGE AND PROMISE OF CELLULAR SYSTEMS BIOLOGY

Cellular function and response lishing causal mechanisms has THE MAJOR mechanisms and pathways. to stimuli are predicated on relied on cellular perturbations, CHALLENGE DNA-based measurements complex interactions between and recent advances in gene-ed- CONTINUES have dominated the omics scene, myriad molecules involving sig- iting with CRISPR technology TO BE THE driven largely by advances in nalling, transcription, genom- have the potential to revolu- INTEGRATION OF next-generation sequencing ic regulation and metabolic tionize our understanding of DATA ACROSS approaches. RNA sequencing processes. Recent advances in molecular causality. THESE OMICS measurements on cells and omics technologies can provide Another challenge in mecha- MEASUREMENTS. tissues have led to tremendous detailed information on molec- nistic systems biology lies in insights into mechanistic cellu- ular components involved in whether the responses of single lar biology; these include time each of these processes. How- cells or a few cells are reflected series and longitudinal measure- ever, the integration of diverse in cell population measure- ments following cellular inputs omics measurements spanning ments. Single cell measurements and perturbations. multiple timescales and coupled are becoming more facile, al- ChIP-seq methods have pro- mechanisms remains difficult. though achieving statistical rele- vided deep insights in transcrip- Biology-agnostic integra- vance will require measurements tional regulatory mechanisms tion of multi-omics data has on hundreds of thousands if not and methods such as ATAC-seq, seldom provided insights, and millions of cells, which is not yet 3-C, 4-C, 5-C and Hi-C meas- contextual analysis anchored on feasible. At the structural level, urements are shedding light on mechanisms, pathways, models crystallography and NMR have chromatin topology changes and and phenotypes remains the made significant methodological their consequences to transcrip- main hope for systems biology. strides, but are still restricted to tion. A number of these efforts While omics measurements single molecule or very simple focus on cancer and stem cell provide large-scale systems-level complexes. CryoEM has made biology. Both proteomics and identification and in some cases substantial advances in deci- metabolomics, which measure quantification of molecular phering structures of assemblies, proteins and metabolites have players, the sequence of events but lacks the ability to capture benefited from advances in mass which gives rise to a phenotype the dynamical mechanisms spectrometry, although the latter continues to be a large chal- involving the molecular players. has the potential to provide lenge. Causality can only be Despite significant challenges, a high degree of quantitation inferred from spatiotemporal mammalian systems biology owing to the existence of isotop- measurements. While temporal has made dramatic advances ically-labelled standards. measurements are becoming and provided deep insights into The major challenge con- feasible in high-throughput biol- collective mechanisms. tinues to be integration of data ogy, spatial measurements con- We describe below the chal- across these omics measure- tinue to remain in the domain of lenges and advances in cellular ments; statistical approaches optics and are not amenable to systems biology, illustrated in correlating properly scaled high throughput. through examples, with empha- multi-omics data are straight- Another approach to estab- sis on reconstruction of causal forward but do not provide

INDIA ALLIANCE 43 10TH ANNIVERSARY EMEI MA, P/C GUY MCLOUGHLIN EMEI MA, P/C

44 INDIA ALLIANCE 10TH ANNIVERSARY

insights into causal mecha- expression to anatomical brain OMICS iological signalling ranging from nisms. Projecting the data onto regions. Distinct omics measure- HAVE MADE visual reception (very short time molecular functions provides ments have disparate time scales BIOLOGY A BIG scales) to mammalian develop- more information, but does not and represent different molecular DATA SCIENCE. ment (long time scales). Dynam- provide causal systems mod- processes, albeit they can have ical modeling of GPCR pathways els. Time-series measurements causal mechanistic connections. demonstrated the interplay be- combined with function or Knowledge of the mecha- tween heterotrimeric G proteins, pathway-based analysis provide nisms or ensuing phenotypes active GPCR, and GTPase acti- insights and hypotheses for can often serve as the basis for vating proteins leading to distinct novel experiments. data integration. For exam- temporally controlled regimes of Omics have made biology ple, systems approaches using GPCR signalling. Such approach- big data science. Each type of longitudinal measurements of es also have promise of feed- high-throughput measurement immune response in diverse back mechanisms, integration characterises, in principle, com- populations of human subjects of signals across multiple time ponents of a cell or tissue. Most across many years revealed scales and modelling response to work in data-driven systems mechanisms that are distinct in transient stimuli in cells. biology identify molecular com- responders and non-responders In developing biochemical ponents using standard tools to influenza vaccination. modeling, extensive utilization of and try to put them into known Known mechanisms in skel- sequence-structure modeling par- context. An example is mapping etal muscle and adipose tissue, adigms offers deep insights. One correlated gene expression data when combined with transcrip- example is the detailed mechanis- on protein-protein interaction tomic and phenotypic data from tic understanding of β-arrestins networks or pathways. The goal normal and insulin-resistant which were originally postulated is to identify genes or proteins patients, identified responders to desensitize activated seven that are co-measured to invoke and non-responders to treat- transmembrane receptors. Using their known biological func- ment. Using functional knowl- omics, protein complex struc- tion. In a systems approach edge of endothelial homeostasis ture and modelling approaches, to prion disease, differentially in combination with RNA-seq, these proteins were shown to be expressed genes between normal ChIP-seq and 4-C data led to the involved in a large number of cell and mouse strain-prion strain discovery of a long coding RNA, regulatory processes. combinations were integrated LEENE, which epigenetically The history of drug discovery with protein-protein interaction regulates eNOS transcription, is founded on development of networks to provide mechanistic thus providing insights into how molecules that target one protein. models for disease. endothelial function leads to But, it is rare that a protein has To facilitate an integrative cardiovascular regulation. only one function or does not access to the large influx of omics Integration of modeling and cross-talk with other proteins, data in the public domain, the experiments in cellular systems leading to off-target effects of Omics Discovery Index (Om- biology has resulted in signif- most drugs. The emerging para- icsDI), an open source platform icant insights into normal and digm is the use of systems biology that enables access, discovery and disease mechanisms. Mathemat- approaches to target a functional dissemination of omics datasets ical modeling of systems uses mechanism, module or pathway was recently developed. Omics standard and complex chemical for therapeutic interventions. data can also be related to normal kinetics, but suffers from the Systems approaches also have the and pathophysiology. One study unavailability of experimentally potential to discriminate between characterized gene expression determined kinetic parameters. responders and non-responders patterns in the regional subdi- Among the most studied cell to drugs and predict drug doses visions of the mammalian brain receptors are G-protein cou- Arun K. Shukla that are physiology-specific, lay- based on the Allen Brain Atlas pled receptors (GPCR) that are Indian Institute of Technology, Kanpur, India ing the foundation for precision Shankar Subramaniam relating cell type specific gene involved in various facets of phys- University of California San Diego. USA medicine.

INDIA ALLIANCE 45 10TH ANNIVERSARY RANDY OLSON/NATIONAL GEOGRAPHIC OLSON/NATIONAL RANDY

46 INDIA ALLIANCE Ajit Lalvani, Srinivas Marmamula, Bharath Holla, and Krishnaveni GV TRANSLATING KNOWLEDGE FOR A HEALTHIER INDIA

Although India has established ical personnel, including research where an exceptional candidate several internationally-recog- nurses, anthropologists, psy- has potential. nised centres of excellence in chologists, dieticians, occupa- Provision of the fellows’ basic biomedical research, trans- tional therapists, dentists and salaries enables IA to stipulate a lation of new scientific discover- optometrists. limit on the clinical and teach- ies into practical solutions for its The spectrum of research is ing duties imposed by the host population’s clinical and public correspondingly diverse, with institutions thereby protecting health needs is rare. projects ranging from laborato- time for research, even in a Despite producing many ry-based translational research to busy hospital environment. The of the world’s best doctors and epidemiological studies, clinical goal of this protected pathway medical academics, India’s trials, health economics and qual- is to enable, for the first time in clinical, translational and itative research to address a very India, clinicians over-burdened public health research activity is wide spectrum of disease areas with the volume of patients to remarkably underdeveloped. To (Figure 1). The common factor pursue their scientific curiosity address this disconnect the India is relevant to the vast disease and develop research ideas. The Alliance launched a new fund- burden of India’s population. Al- fellowships also support at least ing stream in 2013 to support though the first CPH fellowship a year working abroad, promot- clinical, translational and public was awarded just five years ago, ing collaboration with inter- health research. Using the same fellows have already published national scientists, exposure model of early, intermediate and more than 180 peer-reviewed to other research cultures, and senior fellowships as India Alli- papers with 820 citations. The adoption of new technologies. ance's basic science programme demand for the fellowships is ev- Our CPH fellows are the initiative aimed to provide idenced by year-on-year increase pioneers and often based in a career pathway to enable the in applications. institutions with very few if any brightest and best researchers to The high benchmark set by peers or mentors. India Alliance develop into independent inves- the CPH committee for funding and the CPH committee provide tigators, delivering meaningful decisions, informed by detailed great interactive support. The translational outputs. peer reviews from international IA Annual Fellows Conference In the last five years, much experts, fosters excellence which provides a valuable forum in has been achieved. The highly in turn has built a powerful which CPH fellows can interact multidisciplinary, international identity for India Alliance CPH with each another, with basic Clinical and Public Health Re- fellowships. The sequence of fel- biomedical research fellows and search (CPH) Interview Com- lowships provides the long-term with members of the CPH com- mittee has awarded 68 fellow- support necessary to develop mittee who review progress an- ships across 10 states and union the full potential of outstanding Srinivas Marmamula nually and provide mentorship. territories, approximately half of young investigators through to L V Prasad Eye Institute, Hyderabad, India The fellows are also supported Bharath Holla those to women. The committee senior investigator and faculty NIMHANS, Bengaluru, India by workshops on research has funded many non-medics level and beyond. The commit- Krishnaveni GV methodology, grant writing, CSI Holdsworth Memorial Hospital, active in translational or public tee provides constructive feed- Mysuru, India lab management, getting work Corresponding Author: Ajit Lalvani published, public engagement health research, with 36% of the back on applications to improve Director, Tuberculosis Research Centre, fellowships awarded to non-med- weaknesses in an application Imperial College, London, UK and communication skills.

INDIA ALLIANCE 47 10TH ANNIVERSARY

The scope and diversity of fel- low-cost indigenously pro- THE SCOPE AND as well as informal mentorship lows’ research projects is broad duced dental and orthopaedic DIVERSITY OF provided by members of the and impressive. Several fellow- devices and materials. Exam- INDIA ALLIANCE CPH committee. Given the ships address the clinical and ples of translational research FELLOWS' potential of this unique fellow- public health problems thrown include a phase 3 clinical trial RESEARCH ship programme to transform up by the seismic demographic of cancer treatment targeting PROJECTS IS India’s clinical and public health and lifestyle transition of most a leukemic cell-specific genet- BROAD AND research landscape, there is an of India’s 1.2 billion people. ic alteration, the first phase 3 IMPRESSIVE. urgent need to address these Accordingly, several fellow- clinical oncology trial in India. challenges. Removing these ships are focused on chronic The potential benefit of ancient obstacles will pay long-term non-communicable diseases in- Indian practices, such as yoga dividends and unleash the cluding coronary artery disease, and south Indian classical music full potential of the fellowship diabetes, cancer, chronic mental for chronic mental health and programme. health conditions and stroke. neurological conditions are also The next phase of the re- Fellows are also dissecting the being thoroughly assessed. newed India Alliance is substan- metabolic, genetic and lifestyle Clinicians in India face tially increasing funding to the factors, including nutrition, that particular challenges. Fore- CPH stream. This will include predispose the population to most among these is the lack of support for interdisciplinary non-communicable diseases and protected research time. This collaborative clusters to address how these are passed through is being addressed as described priority areas of clinical and generations. Over- and un- above but feedback indicates it public health research. der-nutrition is being addressed may not be enough. Many host This, combined with the at many levels, including pro- institutions do not yet value critical mass of the highly duction and food security. clinical investigation sufficient- skilled fellowship community The huge toll of tobac- ly to protect research time, and their research momentum, co consumption on public which see fellows being drawn could enable us to meet the health is being tackled in back into clinical duties to the aspiration articulated by Dr several dimensions. Commu- detriment of their research and Vijay Raghavan at the inception nity-based trials are evaluating training. More generally, the of the CPH programme: “A the impact of low-cost inter- medical profession does not successful clinical research fellows ventions ranging from mobile value high-quality research and programme can transform India, phone-based technologies to time spent acquiring research and indeed the world”. community-based lifestyle and skills is not recognised by the dietary coaching to prevent bodies conferring accreditation. stroke, heart disease, diabetes There is a lack of any and mental health problems. recognised career track for These studies are taking place in physician-scientists in Indian urban, rural and remote tribal academic medical institutions areas. Vulnerable, under-served which deters many aspiring people including diverse Adivasi clinicians from embarking on a tribal populations and elderly career that includes research. residents of care homes are the A further obstacle is the focus of several epidemiological paucity of expert physician-sci- and interventional studies. New entist mentors to provide approaches to improve diag- inspiration, support and guid- nosis and treatment of major ance. This is being addressed infectious diseases are also being by mandatory inclusion of a developed and evaluated. named mentor when submit- A few fellows are developing ting a fellowship application, Figure 1: Diversity of research carried out by Clinical and Public Health Fellows

48 INDIA ALLIANCE Shweta Khandelwal, Rashmi Rodrigues, and David Osrin

CLOSING THE GAP BETWEEN TOO MUCH AND TOO LITTLE

Indian public health is in transi- Health systems — preventive PLURALISTIC forms including wasting, stunt- tion. Like many sectors, it faces and therapeutic — are them- HEALTHCARE ing, and underweight) remain the duality of want and surfeit. selves fragmented. Pluralistic IS THE NORM, at around 40%, overweight and The historical burden of want, healthcare is the norm, embod- EMBODIED IN obesity are rapidly escalating into manifest in endemic under-nu- ied in beleaguered public sector BELEAGUERED double digits, and all age groups trition and diseases associated care, the traditional fields of PUBLIC SECTOR face multiple deficiencies of with poor water and sanitation, AYUSH (Ayurveda, Yoga and CARE. vitamin and mineral micronutri- clashes with the burden of Naturopathy, Unani, Siddha, ents. Malnutrition is trans-gen- urbanisation, changes in food and Homoeopathy), and a wide erational and the implications for environment, air pollution, in- ranging, weakly regulated, pri- future health and productivity sufficient exercise, and tobacco vate sector providing everything are worrying: 50-90% of women and alcohol use. from primary to super-specialty are anemic during pregnancy The public health picture is care. and 33% of infants have low a composite of epidemiologic The India Alliance is birth weight (<2500 g). Evidence transition and counter-tran- committed to supporting the from other countries shows sition: non-communicable professional and personal that investment in public health diseases, such as diabetes, hy- development of a generation of nutrition research and policy pertension, atherosclerosis, poor scientists who want to address improves productivity and qual- mental health, and longstanding this range of issues in ways that ity of life over a life cycle, and challenges to maternal and new- bring together the old and new, government, funders, and public born health and family plan- that look toward trans-discipli- health agencies have begun to ning, along with communicable narity, and that emphasise the support research to generate diseases, such as tuberculosis, health concerns of the majority. evidence, plan interventions, and newer threats from emerging Through a competitive process, inform policy. epidemics such as Nipah virus the India Alliance selects and Key efforts in the last few and dengue, and antimicrobial supports promising fellows. years include the Niti Aayog resistance. We discuss the work of two, on national nutrition strategy, a Public health measures are nutrition and tuberculosis. mass food fortification initiative, played out with a backdrop of a national food security act, social determinants that also PUBLIC HEALTH the National Health protection reflect a combination of old (the NUTRITION scheme (Ayushman Bharat), and legacy of social divisions) and Although adequate nutrition the National Nutrition Mission new (a widening gap between is fundamental to child health, (Poshan Abhiyaan). rich and poor, environmental growth, and development, India Sustained funding for threats, peri-urban expan- has historically faced challeng- high-quality public health sion, and the advantages and es in public nutrition. Rates of nutrition research and opportu- disadvantages of densification). under-nutrition in children (in nities for researchers at a range

INDIA ALLIANCE 49 10TH ANNIVERSARY ATUL LOKE/PANOS ATUL

of career levels are critical to trial, underway in South India, TUBERCULOSIS improving India’s current health will provide information on With an increase in tuberculosis profile. Shweta Khandelwal is both child development and treatment completion and cure an India Alliance Early-Career other health factors, and is the from 34% in 2000 to 88% in fellow researching maternal and first trial in India to continue 2013, and meeting targets for child health and nutrition at the supplements for women from prevention and control, India’s Public Health Foundation of mid-pregnancy through to six Revised National Tuberculosis India, New Delhi. months of lactation. Program (RNTCP) appeared to She is examining the An India Alliance fellowship be doing well. In 2012, however, effects of long chain omega-3 supports study and provides the Indian government intro- fatty acid (docosahexaenoic mentorship and technical devel- duced mandatory reporting. acid) supplementation, dur- opment in and outside India: a Estimates of numbers of people ing pregnancy and lactation, mix of freedom to develop re- living with tuberculosis in India on infant neurodevelopment. search skills independently and were revised upwards, while This randomised controlled advice that needs calibration. treatment success dropped by

50 INDIA ALLIANCE 10TH ANNIVERSARY

14%. Treatment success also fell globally, and drug resistant tu- berculosis emerged as a serious threat. Amid a sense of global urgency, governments worldwide made commitments to end tu- berculosis. India’s prime minister ANDREW AITCHISON/GETTY IMAGES set a goal to end tuberculosis by 2025, while the global goal is set for 2035. Simultaneously, evidence suggested a need to switch drug-dosing schedules from alternate days to daily. This created logistic difficulty for di- rectly observed treatment (DOT) within the RNTCP and a need to identify alternatives to it. Among other public health researchers, Rashmi Rodrigues, was concerned that reports of tuberculosis outcomes in India did not reflect reality. How- ever, discussions with global health and tuberculosis experts surrounding an evaluation of the RNTCP suggested that it was best left unexamined. There was evidence that prolonged treatment, stigma, and finan- cial constraints interfered with DOT, while private health care added complexity to the Indian scenario. An alternative to DOT was necessary. Having worked a faculty member in communi- NO COUNTRY testing, modification, and large- with mobile phone adherence ty health at St John’s National PROVIDES scale evaluation of population support for long-term treatment academy of Health Sciences, GREATER interventions. No country of infections such as HIV, the Bengaluru, the fellowship OPPORTUNITIES provides greater opportunities challenge of developing similar has helped her to launch an FOR RESEARCH for research across the spectrum interventions for tuberculosis independent research career, ACROSS THE from bench to bedside to body was compelling. Dr Rodrigues establish a research group, SPECTRUM. politic. became interested in the idea disseminate the findings of her of video-based DOT. Her India research, network with interna- Shweta Khandelwal, Public Health Foun- Alliance intermediate fellow- tional researchers, and influence dation of India, New Delhi, India Rashmi Rodrigues, St. John’s National ship is supporting her work on health policy. Academy of Health Sciences, Bengaluru, contextualizing and testing new The India Alliance responds India. David Osrin, University College London technologies for effectiveness to opportunities to change the Institute for Global Health, London, UK and affordability before roll-out face of public health in India Authors contributed equally to the develop- in public health programmes. As through development, rigorous ment of this article.

INDIA ALLIANCE 51 Shahid Jameel and Savita Ayyar

IMPROVING RESEARCH ECOSYSTEMS

When Arun Shukla returned year. A startup ecosystem is put- INDIA PUBLISHES cial management of extramural as an assistant professor at the ting down roots, and academia THE WORLD'S projects, only 18% respondents Indian Institute of Technolo- is building links with industry. SIXTH LARGEST said their institution has a re- gy-Kanpur, he was sceptical Despite these efforts, the NUMBER OF search development office. about staying competitive. Hav- question remains: does India PEER-REVIEWED To compete, Indian insti- ing trained with Nobel Laureates have an enabling environment to RESEARCH tutions must create enabling for his PhD and postdoctoral support researchers like Arun, PAPERS. environments for world-class work in Germany and the Unit- who are returning in growing research. This would involve ed States, Arun worried about numbers? Institutional environ- processes for the recruitment infrastructure, funding, and ments are a mixed bag, with few and assessment of competent opportunities to collaborate in- providing mentorship, flexible and motivated faculty, early-ca- ternationally. Through the years, funding and tenure. Most insti- reer researchers and support his worries have been echoed by tutions are hierarchical. staff; setting up accessible and many researchers returning to A recent survey of scientists affordable infrastructure; and India after training overseas. published in Nature showed developing research manage- India has invested signifi- vast leadership gaps with highly ment capacity and collabora- cantly in building its science variable mentorship, training tions that add value. In such and innovation base: supporting and institutional support. We endeavours, other stakeholders researchers at various career carried out an anonymous such as funding agencies also stages, creating new institutions survey of Wellcome Trust/DBT need to come forward to build and governance systems, offer- India Alliance Fellows to assess partnerships with institutions. ing interdisciplinary research the situation in India. Of the 60 Hiring the right people, who opportunities, initiating large- respondents, only about 50% re- fit the institutional culture and scale infrastructure projects, and ceived formal or informal men- vision, and to mentor, nurture developing high-end research torship and career development and support them with adequate facilities. Today, India publishes support at their institutions. resources, is critical. However, the world’s sixth largest number Significantly, 15% also reported most Indian institutions stand- of peer-reviewed research research misconduct cases in ardize input with varying output papers; these numbers have their labs, which were addressed instead of the other way around. grown at an annual rate of 14% through internal mechanisms. The quality of periodic assess- compared to a global average Our survey also revealed inade- ments is variable, often without of 4%. Though still under 1% quate support for academic lead- a performance-driven system of GDP, science funding has in- ership (40%), lab management of reward or criticism, which creased each year for more than (35%), data management (15%), breeds complacency, except 20 years. A National Postdoctor- research misconduct (58%) where overcome by individual al Programme has taken shape and technology transfer (53%). ambition and brilliance. At India with government funding of Though all institutions in India Alliance too, our ethos is to look 2,500 postdoctoral fellowships a provide some support for finan- hard for the right people, fund

52 INDIA ALLIANCE 10TH ANNIVERSARY

them flexibly and generously, and assess them critically. Our fellows embrace this and make a positive impact by being more critical of their own work, as

well as that of others when they HENRIK5000/GETTY IMAGES serve on review committees.

DIVERSITY IN SCIENCE Ensuring diversity encourages big-picture thinking and intro- duces different ways of achieving excellence. In India while 50% or more science undergraduates, postgraduates and PhD students are women, only about 15% oc- cupy faculty positions in science departments. Intervention is needed to keep women compet- itive as they manage careers and family. At India Alliance due importance is given to career breaks, including maternity leave. Fellows are also given a one-year full cost extension of and ethics. Research manage- GOOD with ways to connect research fellowship following a maternity ment requires blended skills, LEADERSHIP managers locally via online leave. Institutional measures, spanning academic, creative and DEMANDS working groups, courses and such as increasing recruitment administrative functions. Few VISION, AND networking events. An interna- age, time to tenure, and daycare institutions in India have struc- AWARENESS OF tional networking opportunity facilities are needed to make a tured management support. STRENGTHS AND for research managers is show- level playing field. To create awareness about WEAKNESSES. ing best global practices. Formal institutional mech- research management and iden- Most science is technology anisms are needed to support tify opportunities, India Alli- intensive, making it difficult research management and ance recently launched the India for an individual or institution academic leadership. Expecting Research Management Initiative to master or afford everything, a researcher to be entirely self (IRMI). Its focus is to help underpinning the importance managing is often detrimental. institutions share ideas, identify of cutting-edge core facilities, Indian researchers need to be gaps, and find sustainable solu- technical support and collabo- sensitized about new roles that tions. More than 30 institutions rations. Funders must establish help balance the time they spend have formally registered with such facilities and institutions on research and administration. IRMI and several others have require practices that encourage Research management includes reached out. Workshops have their use. Research offices can a set of activities conducted at highlighted issues with sustain- support with raising and manag- the boundaries of research and ability of careers in research ing funds for shared facilities. is now essential for optimal management and the challenges The late management expert, output. These include support to of building formal networks Peter Drucker, once said: “Three identify funding opportunities, and training, given the relative things happen naturally in organ- managing programmes, public scarcity of institutional research izations: friction, confusion and engagement, impact analysis, offices. This is being followed up underperformance. Everything

INDIA ALLIANCE 53 10TH ANNIVERSARY

else requires leadership”. Good research, often without training. skills, and also put young Indian ecosystem is needed for India leadership demands a vision, India Alliance empowers researchers in direct contact to fully participate in global awareness of one’s strengths and researchers into leadership roles with global experts, creating science, through visionary lead- weaknesses, and the ability to in multiple ways. These include opportunities for collaboration, ership, enabling practices, global form partnerships and manage formal training on managing mentorship, and training. visibility, mobility and support conflicts to achieve that vision. budgets, people, and projects. Indian science needs to for building partnerships, the This requires marshalling re- Researchers can seek compet- connect better with global ability to gain and manage fund- sources, whether facilities, funds itive funds to organize public efforts to address problems ing, and public engagement. or people. These skills do not engagement activities and scien- unique to India, but relevant in come naturally to researchers, tific meetings and conferences. the global context, and to ensure Shahid Jameel who take on administrative re- These hone individual com- that research capacity is built in CEO, India Alliance Savita Ayyar sponsibilities in addition to their munication and organizational a sustainable manner. A robust Jaquaranda Tree, Bengaluru, India

Sarah Iqbal and Madhankumar Anandhakrishnan AMPLIFYING THE VOICE OF INDIAN SCIENCE

“A scientist has to be neutral in part. Public communication of POPULAR communicating science to a his search for the truth, but he science is not about marketing SCIENCE broad audience helps scientists cannot be neutral as to the use or PR; it is about humanizing COMMUNICATION get societal perspectives on the of that truth when found. If you science and cultivating a culture IS AS IMPORTANT, relevance of their research, re- know more than other people, of questioning, reasoning and IF NOT MORE tain focus on the big picture, re- you have more responsibility, logic. The aims of such commu- SO, AS ITS fine thought processes, and seek rather than less.” CP Snow nication include, creating aware- SCHOLARLY public partners to solve complex At every point in a scientist’s ness of contemporary science COUNTERPART. problems that affect everyone. career, they must communi- issues, inspiring the next genera- cate their research effectively tion of researchers, enhancing KEEPING THE LINES through academic manuscripts, the relevance and impact of the OPEN IN INDIA funding proposals, conference research, enabling scientists to In spite of a series of recent presentations, public talks, add their voice to public matters local and national-level science representation at institutional and, above all, empowering communication efforts, public and government-level meetings society to take independent communication of science in In- and so on. Communication is decisions on matters that require dia remains peripheral, especially an integral part of a scientist’s scientific knowledge. when compared to leading scien- career and inextricably linked For scientists and research tific nations. Traditionally, scien- to its advancement. As CP Snow funding organizations that dis- tists in India have seldom given decreed, ethical research cannot burse public funds, it is a moral adequate attention to communi- afford to be confined to the lab duty to ensure that the public cating science to their peers and bench or the desk. understands the value of the the public and have generally not Popular science communica- research and its potential impli- considered it as part of their job. tion is as important, if not more cations for society. In addition to However, there have been notable so, as its scholarly counter- these altruistic effects, regularly efforts by government as well as

54 INDIA ALLIANCE ANSHUMAN POYREKAR/HINDUSTAN TIMES VIA GETTY TIMES IMAGES ANSHUMAN POYREKAR/HINDUSTAN

non-governmental organisations course organised by the National THE NEED FOR individuals and organisations and individuals to popularize Centre for Biological Sciences SCIENTIFIC that aim to bridge the science science in the past decades — sci- (NCBS), that has been teaching ENTER­PRISE TO and society gap. ence magazines such as Chakmak the art of popular science writ- TAKE SOCIAL The need for scientific enter- (1985) by not-for-profit Eklavya ing, is yet another example. Since RESPONSIBILI­TY prise to take social responsibili- Foundation, Matchstick Models its launch in 2008, biomedical IS MORE KEENLY ty, is being more keenly felt than and other Science Experiments by research funding agency, Well- FELT THAN BEFORE, before in India, but there is a Dr. Arvind Gupta, Turning Point come Trust/DBT India Alliance BUT THERE IS A long way to go. (1990s), a weekly science show (henceforth India Alliance) LONG WAY TO GO. on Doordarshan, Vigyan Pragati has strived to make its funded HELPING SCIENTISTS TO (Progress of Science, 1952) and research accessible to everyone, SPREAD THE WORD Science Ki Dunia (World of and encouraged and enabled Scientists in India do not receive Science, an Urdu quarterly, 1975) scientists to communicate their sufficient training in commu- by the Council of Scientific & research to the wider public. nication; it is not considered Industrial Research, are examples As well as making all its necessary during their scientific of such efforts. funded research open access, training. Communication ini- In recent times, there have through public lectures series tiatives at national and institu- been significant institutional such as DNA@70, Evolution of tional-level are urgently needed. efforts such as Tata Institute of the Human Mind, and innova- The India Alliance is perhaps Fundamental Research (TIFR)’s tive art and science collabora- one of the first in the country public outreach programme tions like Unseen, Bodystorming to identify this training gap and Chai and Why that not only hits Bengaluru, The Undivided to launch, in 2012, a unique aims to raise public awareness of Mind, Voices for Health, Arting two-day Science Communication science but involves the layman Health for Impact, Actor Doctor workshop in India. It has since, in conversations on science. Project, the India Alliance has trained more than 600 PhD The annual science journalism supported efforts by diverse students, early-career researchers

INDIA ALLIANCE 55 10TH ANNIVERSARY

and clinician scientists. Due to would like to garner trust and Many scientists fear ‘dumbing knowledge and insights to tackle high demand for such training, lasting support for scientific down’ their science for public issues that affect us all. the India Alliance subsequently research. This situation is exac- communication. One way to Public engagement does introduced various one-day erbated by an uneasy relation- encourage the practice of sim- require scientists to shift their variants of these workshops that ship between scientists and the plifying their work would be if attention from research, which have so far trained more than media. Though the dynamic is funding agencies and scientific is unappealing for them. This 2,000 budding researchers in changing, journalists and mass publishers make it mandatory points to a need for communica- the country. Some of the other media in India remain the key for scientists to write accessible tion officers and public engage- initiatives of the India Alliance, source of popular science news. summaries of their research ment practitioners at research such as the Visualising Science There is a long period of when applying for grants or institutions who can make en- workshop with Nature India research before a breakthrough submitting progress reports or gagement time-economical and and FameLab India with the which might pique the interest manuscripts. In India Alliance effective. They can also act as British Council New Delhi, have of the media. It is therefore fellowship applications, such training personnel for scientists encouraged scientists to explore important that scientists get summaries of proposed research and science journalists. creative mediums and innovative people excited about the process are routinely sought. Funded Funding agencies and approaches for communicating of doing science and not just the Fellows are encouraged to sum- institutions should strive to be their work. Recent initiatives of outcomes. marise their published research more supportive of scientists’ the government, such as AWSAR The same is true for fun- in non-technical language; these engagement efforts. Introduc- (Augmenting Writing Skills for damental research, the basis summaries are shared widely ing awards, dedicated funding Articulating Research), a scheme for translational research and through India Alliance’s website for public engagement within to encourage, empower and technological applications, but and social media platforms. large research grants, promise of endow popular science writing attracting much less attention. With more than 20 official protected time within working through newspapers and sites, In light of the digital access and languages in India and many hours for such activity, due magazines, blogs, and social social media, and the rising other dialects, ensuring that recognition of public engage- media, are also a welcome move menace of predatory journals, scientific information reaches a ment initiatives and outcomes in aimed at nurturing the commu- communicating science truth- person in their language, is an overall performance assessment nication skills in young scientists. fully in a timely manner has enormous challenge for scien- for promotions and meritorious become even more important, to tists and science communicators awards, tangible opportunities SOCIETY'S ACCESS counter the spread of misinfor- in India. There have been local to inform policy through their TO KNOWLEDGE mation and false news. initiatives, but concerted and work, possible incentives. In some of India Alliance’s Introducing Science Media sustained efforts are needed to Conscious and co-ordinated public engagement outings, and Journalism Fellowships build capacity for quality science effort to include as many stake- participants have expressed a could help scientists and jour- communication in regional holders as possible in the pro- wish to know what scientists are nalists understand each other’s languages in India. cesses of scientific discovery and broadly working on, and how process of enquiry and collec- policy deliberation will go a long that research will help society. tively explore ways to engage the ENGAGING WITH SCIENCE: way in ensuring due considera- Public access to science is defi- public with science. THE WAY FORWARD tion of multiple key viewpoints. cient in India. It is as if the walls Citizen science projects have The India Alliance remains around research institutions are LINGUA FRANCA: FINDING been initiated around the world, strongly committed to devising proving to be both literal and COMMON LANGUAGE in which public can meaningful- and implementing mechanisms figurative barriers. Perhaps one of the biggest ly contribute to current research, to broaden the voice of Indian Mostly, the public simply challenges for Indian scien- rather than as passive recipients science, nationally and wants to understand how the tists is the language of science. of information. Unfortunately, internationally. scientific research will impact Scientists are increasingly most public outreach events in their lives — the purpose and specialising, making it difficult India are designed as a one-way Sarah Iqbal Public Engagement Officer, not the complex details of the for them to process, and then passing of information. Public Wellcome Trust/DBT In­dia Alliance. [email protected] science. Providing this access communicate their research engagement is supposed to be a Madhankumar Anandhakrishnan, is particularly important if the within a broader context, some- two-way process, in which the Grants advisor, Wellcome Trust/DBT India Alliance scientific community in India times even to their own peers. scientists and the public share [email protected]

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