PAWAN GOENKA on India As an Innovation Hub

INTERVIEW KRIS GOPALAKRISHNAN

SHAASTRAMAG.ORG

VOLUME 01 | EDITION 01 | MAY-JUNE 2021 | `199 SCIENCE | TECHNOLOGY | INNOVATION FUTURE VACCINES A clearer understanding of the SARS-CoV-2 virus could lead Indian biologists to develop more potent vaccines. + Gennova brings mRNA home + Mynvax: A vaccine ‘made’ for India

PAWAN GOENKA on India as an innovation hub

The emerging ecosystem for BIOTECH START-UPS

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SHAASTRA 2021 May-Jun 14.indd 2 5/18/21 7:26 PM 03 Letter from the Editor Contents 04 What Shaastra is about 06 News in Brief A round-up of recent advances 2021 may-jun across science domains. VOLUME 01 EDITION 01 SOXWHITE / 123RF 11 Why physicists are astir Learnings from the muon g-2 experiment.

12 The ‘efficiency trap’ Guest Column: Guru Madhavan

shaastramag.org

Supported by the 50,000-strong alumni of IIT Madras.

Editorial 14 The joy of learning science Editor Guest Column: Ramji Raghavan Hari Pulakkat Executive Editor Venky Vembu 16 The chips are up Vaccines of the future 20 A new dawn is breaking Contributing Editors K.C. Krishnadas for Indian chip design and Gauri Kamath A clearer understanding of the SARS-CoV-2 virus could lead manufacturing, but old T.V. Padma Indian biologists to develop more potent vaccines, in quick time, challenges remain to be in response to the pandemics of the future. Hari Pulakkat offers a overcome. — K.C. Krishnadas Editorial Board glimpse of what is to come. S. Vedantam B.S. Murty COVER STORY H.S.N. Murthy FUNTAP / 123RF 20 Tomorrow’s vaccines J. Tripathy Indian biologists are working R. Rengaswamy to understand the coronavirus K.M. Sivalingam G. Jayaraman better, and are hoping to use H. Ramachandran that knowledge to develop better D.K. Chand vaccines for the future. Hari U. Dash Pulakkat surveys the scientific R. Rama Y. Shanthi Pavan landscape. B. Santhanam NAMAS BHOJANI

Design Pranab Dutta Rakesh Kumar Manish Pratap Singh

Published by IIT Madras, India as an innovation hub 35 Chennai 600036. Editor: Hari Pulakkat Guest columnist Pawan Goenka reasons that the post-COVID geo- economic landscape presents India with a godsent opportunity for Indian manufacturing to demonstrate its prowess. Advertising enquiries [email protected] 26 Heat and dust JIGNESH MISTRY Manupriya reports on a Subscription enquiries COVID-19 vaccine developed by [email protected] a biotech start-up incubated at Letters to the Editor IISc, which is uniquely suited for [email protected] Indian conditions.

Copyright: IIT Madras. 28 Life-saving messengers All rights reserved Two scientists, across continents, throughout the world. collaborated to bring the mRNA Reproduction in any vaccine to India. The technology, manner prohibited. adapted for COVID-19 times, could open up new opportunities to treat other killer diseases. Cover Design PealiDezine 30 Nimble Niramai Photos Fab labs of drug discovery 38 Jayadevan P.K. profiles a health Shutterstock, tech start-up that innovatively Rawpixel, WEF Indian start-ups are venturing into the high-risk, high-attrition secured a lifeline when COVID pursuit of new drugs, enabled by an emerging ecosystem. Gauri struck. Kamath ventures into the brave new world of biotechpreneurs. 1

SHAASTRA 2021 May-Jun 14.indd 1 5/18/21 7:26 PM Contents BIG DATA KANNAN KRISHNAMURTY 32 Short on innovation How India fares on the Global Innovation Index, and what it will take to vault into the Big League.

35 It’s time for India to shine Guest Column: Pawan Goenka

SPECIAL FEATURES 36 Order from complexity How Prof R.I. Sujith of IIT Madras is using complex systems theory to ensure smooth functioning of gas turbines and rocket engines. — Aditi Jain

38 Boost for biotech start-ups Indian start-ups are venturing into the high-risk, high-attrition pursuit of new drugs, enabled by an emerging ecosystem. Gauri How to put out a fire 36 Kamath ventures into the brave How a ‘Eureka! moment’ led Prof R.I. Sujith to solve the problem of new world of biotechpreneurs. ‘combustion instability’. By Aditi Jain.

BENEDIKT VON LOEBEL/WEF

42 Rx for safer drugs Scientists at IIT Kanpur uncover a protein mechanism that holds promise for regulating drug effects, reports Adita Joshi.

44 Think big Interview with tech investor and philanthropist Kris Gopalakrishnan on science, society, and philanthropy.

46 Zeroing in on zero waste Technological interventions are ‘Set ambitious project goals’ 44 coming to the aid of solid waste management in Indian cities, Interview with tech investor and philanthropist Kris Gopalakrishnan reports T.V. Padma. on the wisdom of thinking big on research and programmes. 50 How green is my village? NIDHEESH M.K. Meenangadi in Kerala points the way to a carbon-neutral future. A field report from Nidheesh M.K.

54 BOOKS Reviews of Mariana Mazzucato’s Mission Economy; Krish Ashok’s Masala Lab; and Tom Higham’s The World Before Us

60 FIRST PRINCIPLES Explainer: The Standard Model of particle physics

62 FUNTECH Science/technology-themed puzzles

64 TIME MACHINE It only takes a village 50 1971: Technology in the Harnessing technology, and drawing on enlightened ecological rear-view mirror policies, Meenangadi in Wayanad district of Kerala is on the path to becoming India’s first carbon-neutral village. ByNidheesh M.K. 2

SHAASTRA 2021 May-Jun 14.indd 2 5/18/21 7:27 PM Letter from the Ideas that will Editor shape our future

will become even more crowded, creating enormous amounts of waste. New diseases will emerge as the earth warms up Hari Pulakkat and people live in overcrowded surround- ings. Amidst all this, the country has to create economic growth and provide jobs to three-fourths of its population. We will track and interpret the impact of these PANDEMIC is the worst and events on our country. But since we believe the best of times to launch a sci- in science and technology as a force for ence and technology magazine. positive change, our stories will focus on It is the worst time because pub- solutions rather than problems. lic attention is largely focussed The story on Page 38 by Gauri Kamath oAn survival – and not on reading a freshly is about how a good ecosystem is emerging minted magazine. But it is also the best for drug discovery start-ups, which are dis- time because the public is interested in covering products that large pharmaceuti- reading about science more than ever, and cal companies were unable to do. On Page a specialised product can dive to a depth 46, T.V. Padma writes about technological that a general interest publication cannot. solutions to the mounting solid waste in The pandemic had been in full swing for cities. K.C. Krishnadas reports on Page 16 nearly a year when we started preparing about how conditions provide India’s com- seriously for our inaugural issue. Events panies one more opportunity to create a had made the choice of our cover story au- large fabless semiconductor industry. And tomatic. But considering the long shelf-life on Page 50, Nidheesh M.K. reports on how and specialised nature of our magazine, a village in Kerala is faring on its journey we chose a topic not yet covered in the me- to become carbon-neutral. dia. What are scientists doing in their labs The columnists in the magazine have that will result in improved vaccines capa- been chosen with care from some of the ble of eliminating the pandemic? The an- best minds in the country and abroad. On At Shaastra, we swer to this question was not easy to find Page 35, Pawan Goenka, Chairman of the believe in science and in India, but after searching hard, we Board of Governors of IIT Madras and IIT dis-covered some work that looks Bombay, describes how India can create technology as a force promising. It is our first cover story. an innovative manufacturing ecosystem As a magazine, we will always be look- by moving away from the incrementalism for positive change. Our ing for ideas that will create our future. At of the past. Ramji Raghavan, founder of stories will, therefore, the moment, a good COVID vaccine is as Agastya International Foundation, writes important as any idea. To the cover pack- on Page 14 about how ‘creative learning’ focus on solutions age, we also added stories about two Indian is a necessity and not a luxury for the un- companies about which we will hear a lot derprivileged. On Page 12, author and en- rather than problems. soon: Gennova and Mynvax. Gennova is 15 gineer Guru Madhavan writes about how years old and had functioned as a public- attempts at efficiency can go too far and ity-shy biotech company, but the pandem- become counter-productive. ic pushed it right to the forefront of our On Page 44, Infosys co-founder and battles. It is developing India’s first mes- philanthropist Kris Gopalakrishnan talks senger-RNA vaccine; our story is about its about funding science to create an inno- history and the events that drove its evolu- vative economy. It is the first of our in- tion as a vaccine company. The third part terview-podcasts that we will host on our of our cover package, about the start-up website. Mynvax, grew out of our first story. Myn- Our books pages are not just for review- vax was founded by two seasoned profes- ing books, but a platform for writers to ex- sionals: an entrepreneur who has already plore powerful new ideas. In this issue, we sold a successful venture and a professor have books on how governments can accel- at the Indian Institute of Science. Mynvax erate economic growth through moonshot develops a vaccine that kills two birds at projects, and how research is revealing a one stroke: flu and COVID. new story about human origins. A third re- Elsewhere in the magazine, we look at view is about the science of food and how stories that have long-term significance for we need to understand how we cook what the country. In the next few decades, like we eat. the rest of the world, India will increasing- Enjoy our inaugural issue. ly face the impact of climate change. Cities Hari Pulakkat 3

SHAASTRA 2021 May-Jun 14.indd 3 5/18/21 7:27 PM Why Shaastra? Why IIT Madras? Why now?

nology. From zinc extraction to civil engineering marvels, our medieval engineers developed a deep understanding of science – from microstructure of materials to quakes – and ensured that society benefited from these discoveries. They also established a communication tradition that ensured con- tinuity. As Prof. M.S. Sriram, an academi- Mahesh V. Panchagnula is the Dean cian who founded the K.V. Sarma Research (Alumni and Corporate Relations), IIT Foundation points out, this could not have Madras, a Professor in the Department been possible without a healthy conferenc- of Applied Mechanics – and the impetus ing of people from academia and industry. behind the Shaastra project. However, over the last century, that communication channel has broken down, and URING THE recent fourth Test the two have evolved silos of their own. An match between India and En- illusional mismatch in expectation times- gland, there was one brief mo- cales then manifests itself: industry, it is ment that became a metaphor said, talks quarters, while academia talks for something larger than crick- semesters. These untruths need to be rem- evant problems and being industry-facing. Det. It happened when Rishabh Pant and edied immediately. Shaastra is an attempt Several industry partners acknowledge IIT Washington Sundar were at the crease: to bridge this communication gap. Madras’ contributions to their technolo- two youngsters taking on an experienced Any successful technology development gies. The cherry on top is the IIT Madras English attack. James Anderson, argu- requires three attributes: the will and the Research Park, the country’s oldest and ably one of the world’s best bowlers today, confidence to get started; the knowledge of most active, which is home to 700 industry came charging in with the second new how the task can be executed; and the skill partners and young start-ups collocated ball. Facing the first ball, Pant stepped and dexterity to see that knowledge flow and driven by a desire to collaborate with out of the crease – as if he were playing into action. Our space program is illustra- IIT Madras faculty and students. a T20 match – and walloped Anderson to tive of this. In the 1980s, SLV was mischie- Shaastra has been IIT Madras’ long-run- the fence. The perfection of that shot, and vously expanded as Sea Landing Vehicle ning annual technical festival, celebrating the two youngsters’ body language all owing to multiple failed launches. But the spirit of engineering and innovation through their innings, summed up, in my that did not deter our space scientists from through various competitions, summits, mind, what India has become in the last continuing their trials. In due course, SLV lectures, exhibitions, demonstrations, and decade: a self-aware and self-confident, yet came true to its name: Satellite Launch workshops. Few institutions other than IIT humble, young country. Vehicle. Only a handful of countries in Madras have the gravitas, the credibility, That leads us to the story of the gene- the world have this technology today – not and the objectivity to comment on technol- sis of Shaastra, the magazine you hold in because the others lack resources, but be- ogy trends in the industry. Shaastra is en- your hands. cause they lack one of the three attributes visioned to be a curated voice articulating required. Conversely, countries that have the cutting-edge of science and technology WHY SHAASTRA? developed space access technologies have in India in a language that both industry Science and technology infrastructure all three traits – and, additionally, a well- and academia will absorb and value. in India has expanded dramatically in the evolved academia engaged in research, past 10 years, but to make sense of what is as well as a busy exchange of people and WHY NOW? happening, and distill its implications in ideas between academia and industry, as Because the Rishabh Pant metaphor ap- language that is easy for readers to com- was the case in medieval times, when In- plies to India in other domains as well. prehend, requires a sophisticated under- dia was a technological superpower. To India is home to crores of young, well- standing. That perhaps accounts for why get India back into a leadership position in trained technologists who are determined science and technology media products are the science and technology realm, it is crit- to script their own destiny. They have ac- somewhat sparse in the media landscape. ical to get this academic-industry interface quired the first two of the three attributes A recent survey by the IIT Madras Alumni humming again. Shaastra aims to be a cat- required for technology development, and Association suggests that over 90% of the alyst in that dynamic process. are poised for take-off. There is, thus, a public are happy to share science and tech- fierce urgency to the present moment. nology findings on social media, if they are WHY IIT MADRAS? Shaastra is seizing this optimal moment presented as a digestible byte. Shaastra, IIT Madras has, over the past 60 years, to fulfill the demand for a science and tech- which comes with an IIT Madras pedigree, evolved into an institution of national im- nology magazine in the media landscape. is an endeavour to fill that vacuum, both in portance and an Institute of Eminence. It In classic Pant fashion, we’re hoping to the print and digital space, primarily in the has been the #1 ranked Engineering Insti- knock this one out of the park. Stay tuned! interest of enhancing an understanding of tution in the country for five successive science and technology. years. This string of stellar achievements This vacuum is doubly puzzling, given is in no small measure due to the DNA that that India has a long tradition of scientific IIT Madras’ German founders infused into discoveries that have translated into tech- it: a culture of working on industrially rel- Mahesh V. Panchagnula 4 A boy reads one of the 650,000+ books made accessible to people with print disability under the Sugamya Pustakalaya program, a joint effort between TCS Research, Daisy Forum of India, and National Institute for Empowerment of Persons with Visual Disabilities, Government of India.

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SHAASTRA 2021 May-Jun 14.indd 5 5/18/21 7:27 PM News in Brief Borophane, the new ‘wonder material’, is here MARK HERSAM/NORTHWESTERN UNIVERSITY MOVE OVER graphene: boro- borophene out of the ultrahigh phane, considered a ‘wonder vacuum and into air, it immedi- material’ of sorts, is here, and ately oxidises. Once it oxidises, could potentially revolutionise it is no longer borophene and is batteries, electronics, sensors, no longer conductive. The field photovoltaics and quantum will continue to be hindered in computing. Created by bonding exploring its real-world use un- atomic hydrogen with a sin- less borophene can be rendered gle-atom-thick sheet of boron, stable outside an ultrahigh vac- borophane is not just stable at uum chamber.” standard temperatures and air Although borophene is pressures, but also has high frequently compared to its mechanical strength, flexibility super-material predeces- and superconducting proper- sor graphene, borophene is ties. much more difficult to create. Before borophane, there Graphene is the atomically thin was borophene, an analogue version of graphite, a layered of graphene, which was once material comprising stacks of hailed as a wonder material. two-dimensional sheets. To re- The quest for more graphene- move a two-dimensional layer like two-dimensional materials from graphite, scientists simply prompted physicists to predict peel it off. in the 1990s that boron atoms, Boron, on the other hand, is too, can form a monolayer not layered when in bulk form. through computer simulations. Five years ago, Hersam and col- However, it was synthesised laborators created borophene only in 2015. for the first time by growing it SED CONGUE EROS Studies have shown boro- directly on a substrate. The re- phene to be stronger, lighter and sulting material, however, was more flexible than graphene. An artist’s illustration of borophane. The teal balls represent highly reactive, making it vul- But borophene has a fundamen- boron atoms; the red balls represent hydrogen. nerable to oxidation. tal problem: it can only exist Now that borophane can be inside of an ultrahigh vacuum computational materials science research- taken out into the real world, chamber. And this limited its practical er at Argonne National Laboratory and at Hersam said researchers will be able to use outside the lab. Now, a team of mate- the University of Florida. The team report- more rapidly explore borophane’s proper- rials researchers led by Mark Hersam at ed the synthesis of borophane in a paper ties and its potential applications. Northwestern University in Illinois has published in Science journal in mid-March. “Materials synthesis is a bit like bak- overcome this problem by depositing atom- The scientists claimed that borophane ing,” Hersam said. “Once you know the ic hydrogen onto borophene’s surface to has the same exciting properties as boro- recipe, it’s not hard to replicate. However, develop borophane. phene and is stable outside the vacuum if your recipe is just a little off, then the Among Hersam’s collaborators is Venkat chamber. Hersam, who is also director of final product can flop terribly. By sharing Surya Chaitanya Kolluru, a B.Tech from the Northwestern University Materials the optimal recipe for borophane with the the Indian Institute of Technology (Indian Research Science and Engineering Center, world, we anticipate that its use will rapid- School of Mines) Dhanbad, and a graduate explained: “The problem is that if you take ly proliferate.” 7 The promise of biodegradable ‘aquaplastic’

AN ESTIMATED 335 million tons of plas- biodegradable bioplastic processed with standing strong acids, bases and organic tic is produced annually the world over, water. The researchers, some of whom solvents. causing potentially irreversible damage to have an Indian connection, have coaxed a More importantly, unlike conventional the environment because plastic is largely genetically engineered common bacterium plastics, which require thermomoulding, non-biodegradable. Bioplastics are some- – E. coli – to produce long protein nanofi- hydrogels made of these protein nanofibres what more eco-friendly, but they constitute bres that can be cast and dried to create a can be moulded, welded and healed by wa- less than 1% of the total plastic production. plastic with mechanical properties similar ter, earning it the sobriquet ‘aquaplastic’. Now, scientists in the US have fashioned to those made from petrochemicals. The scientists, led by Neel Joshi at North- a new class of microbial biofilm-based The new material is also capable of with- eastern University in Boston, reported the 6

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A schematic of aquaplastic fabrication from genetically engineered bacteria programmed to produce a functional curli fiber-based aquagel that can be moulded into 2D and 3D architectures.

findings, which are largely a proof of -con The work on aquaplastic, in fact, began “This is a problem we are working on, try- cept, in a paper published in Nature Chem- earlier, when Joshi was with Wyss Institute ing to leverage the customisability of Aqu- ical Biology journal. for Biologically Inspired Engineering at aPlastic to imbue it with water-resistant “Our material combines several proper- Harvard University. He and his postdoctor- properties,” Joshi said. “There are some ties that are useful in the context of bioplas- al fellows – Anna Duraj-Thatte and Avinash immediate applications that we are pursu- tics,” said Joshi, the principal investigator Manjula-Basavanna – also first authors of ing. Some polymers (such as polyvinyl alco- for the study. “It is made from a biological the paper, observed that when these hydro- hol) are designed to be water-soluble. PVA system, it is biodegradable, and it can be gels produced by genetically engineered E. forms the pouch that dishwasher detergent customised for specific performance appli- coli are cast and dried under ambient con- pods come it, for example. Although PVA is cations. There are few bioplastics that are ditions, they can become plastic with me- soluble, it is not very biodegradable. Aqua- both made from biology and biodegradable – chanical properties comparable to those of Plastic could replace PVA with a biodegrad- only those based on starch or certain polyes- conventional plastics. able alternative,” he added. ters (for example, polyhydroxyalkanoates). Joshi, who grew up in the US but has roots Manjula-Basavanna, who did his PhD at None of the existing polymers can rival our in Mumbai, acknowledged, however that the Jawaharlal Nehru Centre for Advanced protein fibers in terms of molecular custo- in its current state, aquaplastic will swell Scientific Research, in Bengaluru, said the misability, which will be advantageous for and rehydrate in water, making it inappro- researchers are confident that AquaPlastic achieving different performance character- priate as a replacement for many types of can find potential applications in primary istics,” Joshi said. plastic (for example, as water bottles). packaging and protective coating. 7 Mimicking photosynthesis to produce fuel

LUMUT/123RF RESEARCHERS at the Bengalu- hydrocarbon fuels through an es- ru-based Jawaharlal Nehru Centre tablished industrial process called for Advanced Scientific Research Fischer-Tropsch synthesis. (JNCASR) may have designed an arti- If carried out at commercial scale, ficial system that mimics how plants such technology interventions can and other photosynthetic organisms help solve two intractable problems use sunlight to convert atmospheric faced by humankind. Once such carbon dioxide and water into mole- technologies are perfected, they can cules that can be used as fuel. help sequester carbon dioxide emit- Still in an early stage of develop- ted into the atmosphere due to in- ment, the artificial photosynthetic dustries and fossil fuel use and thus system developed by a team led by reduce problems precipitated by cli- JNCASR professor Tapas Kumar mate change. Second, they can yield

Maji can capture CO2 from the at- greener ways to produce fuels. But mosphere and convert it into carbon they still have a long way to go before monoxide which can be used as fuel they become economically viable. in internal combustion engines. The system was reported in a pa- Typically such systems, as in per published in Energy and Envi- plants, work through two linked ronmental Science journal in early chemical reactions: one that splits March. The integrated catalytic sys- water into protons and oxygen gas, tem that they developed is based on

and another that converts CO2 into a metal-organic framework (MOF- CO. CO can then be converted into 808) comprising of a photosensitiser 8

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SHAASTRA 2021 May-Jun 14.indd 9 5/18/21 7:27 PM News in Brief (a class of molecules that absorb light and nanospace of MOF-808. When both these assembly does not participate directly in transfer electrons from the incident light molecular entities stay in close proximity chemical reaction, it can be reused for sever- to nearby molecules) and a catalytic centre in the confined space the porous MOF-80, al cycles without any loss in its activity.

that can eventually reduce CO2 to CO. there could be an excellent uptake of CO2 The JNCASR team believes this intricate To do this, the scientists kept the pho- at room temperature. design and approach will pave the way to tosensitiser, a chemical called ruthenium According to the scientists, the catalyst develop new integrated catalytic systems

bipyridyl complex, and the catalyst, an- showed excellent ability to reduce CO2 to CO. to capture CO2 and convert it into different other chemical called rhenium carbonyl It also split water to produce oxygen. They energy-rich chemical feedstocks by mim- complex, closer to each other inside the also found that as the integrated catalytic icking photosynthesis. 7

VLADIMIR SALMAN/123RF eas where contaminated drinking water is a serious issue. They are also making the design of the filter freely available to anybody interested in making such filters, including entrepreneurs and civil society or community organisations working with people living in areas with poor quality of water. To make these filters work, the MIT researchers had to overcome some of the natural limitations faced by sapwood once it dries up. For instance, when the wood dies up, the sieve-like membranes begin to stick to the walls, reducing the filter’s ability to allow water to flow through. Besides, the build-up of woody matter inside can also clog the conduits. The researchers overcame these limitations through two simple treatments. They first soaked small cross-sections of sapwood in hot water for an hour and dipped them subsequently in ethanol. Once it dried, the material is capable of retaining its permeance as good as commercially available filters, they found. The researchers who worked on the xylem filers include Krithika Ramachander, Megha Hegde, Anish Antony, Luda Wang, Kendra Leith and Amy Smith. This research was supported, in part, by the Ab- dul Latif Jameel Water and Food Systems Pinewood stems as cheap Lab at MIT and the MIT Tata Center for Technology and Design. Once satisfied with the performance of water filter systems the filter in the lab, the researchers tested the filter – made using locally available CAN TREES like pine yield an efficient from drinking water. Further, they devised wood – in communities in the Himalayan water filtration system that can reduce the simple techniques that can extend the fil- region as well as in a low-income urban set- disease burden associated with contami- ter’s shelf-life, enabling the woody disks tlement in New Delhi for two years. nated drinking water? A team at the Mas- to purify water after being stored in a dry Based on feedback from over 1,000 poten- sachusetts Institute of Technology (MIT), form for at least two years. The scientists tial users across India, the MIT engineers which includes many India-born scientists, demonstrated that the filter can work in re- designed a prototype of a simple filtration may have tapped the ability of stems of al-world situations by carrying out trials in system, fitted with a receptacle at the top non-flowering trees like conifers to work as India by purifying water from contaminat- that users can fill with water. The water natural sieves. ed spring, tap and groundwater sources. flows down a 1-metre-long tube, through a The interiors of these trees contain The low-tech design was further perfect- xylem filter, and out through a valve-con- straw-like conduits known as xylem, which ed based on feedback received from users trolled spout. The xylem filter can be draw water up through a tree’s trunk and in India, leading to development of a pro- swapped out either daily or weekly, depend- branches. These conduits are interconnect- totype of a simple filtration system, fitted ing on a household’s needs. ed through thin membranes for filtering with replaceable xylem filters. This low- The team is exploring ways to produce out bubble from water and sap that pass cost water purifying system, capable of xylem filters at larger scales, with local- through. Exploiting this natural filtering giving potable water at a rate of one litre ly available resources and in a way that ability of sapwood, engineers led by Ro- per hour, was reported in Nature Commu- would encourage people to practise water hit Karnik, professor of mechanical engi- nications journal in late March. purification as part of their daily lives -- neering at MIT, fabricated filters that can The scientists are now looking to make for instance, by providing replacement fil- remove pathogens like E. coli and rotavirus these filters available at large scale in ar- ters in affordable, pay-as-you-go packets. 7 10

SHAASTRA 2021 May-Jun 14.indd 10 5/18/21 7:27 PM ON OUR RADAR A WOBBLE HAS PHYSICISTS ASTIR REIDAR HAHN/FERMILAB First results from Fermilab’s muon g-2 experiment hint at new physics, but the jury is still out on the final findings.

HARINI BARATH

HE FIRST week of April was a mo- mentous one for particle physicists. Scientists at the Fermi National Accelerator Laboratory in Illinois Tconfirmed earlier findings that elementary particles, called muons, are more magnetic than expected, deviating ever so slightly from the expected theoretical prediction. This tiny discrepancy could be a sign of new physics, scientists say, perhaps an unknown force or new particle that subtly influences the muon’s magnetic behaviour. Muons are subatomic particles very sim- The muon g-2 ring at Fermilab. ilar to electrons, but 200 times more massive and highly unstable. The Fermilab ical tweaks would allow scientists to make vious measurement was really exciting,” muon g-2 (read ‘g minus two’) experiment a more precise and reliable measurement. concurs Labounty. essentially measures, very precisely, how The first run of data collection that culmi- magnetic muons are. It is a long-awaited nated in the recent announcement took WHAT THIS MEANS sequel to a measurement of the muon’s place in 2017 and 2018. Two more runs have This meant that the minuscule discrepan- magnetic field done at Brookhaven Nation- been completed since, and a fourth run is cy between theory and experiment stands. al Laboratory, New York, in 2001. In both under way. The goal is to improve the mea- “The difference is not large enough for us experiments, muons sped around a large, surement’s precision by a factor of four. to claim that new physics has been dis- doughnut-shaped magnet (15 metres in di- For their part, theoretical physicists covered, but it is intriguing and hearten- ameter) in which the magnetic field makes have been busy crunching the numbers ing that it has remained,” says Thomas them spin like tops. The more magnetic while the muons race around the ring. In Teubner, a theorist at the University of they are, the more they wobble or precess 2016, Aida El-Khadra, a particle theorist Liverpool and a member of the Theory Ini- as they spin. The strength of its magnetic at the University of Illinois, worked with tiative. While other claims that challenged field or “magnetic moment” is measured others to organise the Theory Initiative, the Standard Model have come to nought, by a quantity called the ‘g-factor’. an international consortium of 132 theo- the muon g-2 discrepancy continues to According to the Standard Model of par- retical physicists who collaborated to nail hold promise for new physics beyond the ticle physics, currently the most reliable down a theoretical Standard Model predic- Standard Model, he says. theory describing the subatomic world, tion of the g-factor. The magnetic moment On the other hand, a Nature paper pub- the muon’s magnetic moment is very close, of elementary particles is affected by fleet- lished on the same day as the Fermilab an- but not equal, to 2. Twenty years ago, the ing “virtual” particles that they constantly nouncement has dampened the excitement Brookhaven experiment found that the dif- emit and reabsorb. The contributions from for some. Calculations by a team of theo- ference, g-2, was slightly bigger than what all known particles are tallied up to arrive rists called BMW reported a predicted val- theory indicated at the time. “It was the at the minute deviation of the muon’s mag- ue that is much closer to the experimentally first tantalising clue that something was netic moment. Last summer, the Theory measured magnetic moment. The approach missing from the theoretical calculation,” Initiative reported the predicted value in a used in the BMW calculations is relatively says Priscilla Cushman, a member of the white paper and waited with bated breath new, and different from the one adopted by Brookhaven Muon g-2 team, now a profes- to see if the experimental result would dis- the Theory Initiative. The latter is time-test- sor at the University of Minnesota. Even agree with the calculations once again. ed and has been refined over decades by though the 50-year-old Standard Model has Given COVID-19 limitations, the results many different groups. The BMW study successfully explained the fundamental were unveiled to over 200 physicists on a must be taken seriously, but it is premature particles and forces that make up the uni- private Zoom call in late February. The to take it at its face value, insists El-Khadra. verse, it falls short in many ways. It does final value of g-2 depended on a number Independent calculations from other teams not explain dark matter and dark energy from a precise clock that was kept secret that use the BMW approach are needed to and does not account for neutrino masses while scientists were gathering data and confirm, or challenge, the robustness of or even gravity. We know that the Standard doing their analyses. This number was un- that claim. As experimentalists continue to Model is not perfect and we have to modify veiled live on Zoom and plugged into the churn out ever-precise measurements, the- it, but we don’t know how, says Cushman. calculations. Members of the Fermilab orists have their work cut out as they weigh Measurements that contradict theory are team and University of Washington grad- competing theories. “This is not the end of exciting because they hint at where the uate students, Brynn MacCoy and Josh- the journey by any means,” Teubner sums theory is lacking, she says. ua Labounty were among those present. up. “I see these results as important mile- The giant magnet was subsequently “I was holding my breath,” says MacCoy. stones along the way.” 7 transported to Fermilab, where a more “Seeing the final value of g-2 pop up on powerful muon beam and other technolog- screen and agree so closely with the pre- See also: Page 60 444 11

SHAASTRA 2021 May-Jun 14.indd 11 5/18/21 7:27 PM TINKER, TAYLOR, SOLDIERING, SPY Efficiency may seem to enhance productivity, but in practice it does not offer an unalloyed advantage.

MANISH PRATAP

Guru Madhavan

OHN LE CARRÉ laid espionage traps. They came with honey pots, false flags, Jand negotiated morals. Just as in these thrillers, one such ‘double agent’ has infil- trated vast areas of our real lives: the concept of efficiency. We created efficiency as a way to think about reducing waste and boosting performance. Now with untold variants, efficiency has become much more insidious. What was once a solution to es- cape the trap of disorder has now become the trap itself. The world is full of examples where the ‘efficient’ solution In the frosty January of 1912, a perfect- had monstrous consequences ly accoutered Frederick Winslow Taylor appeared at a congressional hearing in scale to produce it in sufficient quantity, and or less a scripted show. We buy into the un- Washington, DC. Over four days, with for- the only product it could provide was coiled, spoken theory that these optimise billable mulas and charts, the steely-eyed engineer which was incompatible with the assem- hours while leaving our work environments lectured politicians on process control, cap- bling equipment. Unspooling dramatically increasingly less nurturing, an enemy of italism, and work philosophy. A year earlier, slowed production. Policy wonks “wouldn’t productivity and creativity. he had published The Principles of Scien- classically think we needed to produce elas- The third is when efficiency is viewed as tific Management, an accidental bestseller. tic,” Fuchs points out. “And yet, in this sto- a tradition. Efficiency can be a fierce num- Taylor sold his theory as the way to elevate ry, that lack of elastic cost our country mil- bers game. A ritual in its own right, effi- efficiency in “every branch of the business lions of masks a week.” ciency thrives on rigidity, repetition, and to its highest state of excellence, so that the The point here is not to make elastic man- rigour. A penchant for quick returns un- prosperity may be permanent.” ufacturing a national priority, but to make wisely erodes investments in not just main- Taylor’s ideas spread from the oily ma- the manufacturing system itself more elas- tenance and scientific research but civics chine shops of Pennsylvania to the cham- tic. Piecemeal efficiencies (or inefficiencies) and arts as well. Yet we consciously make bers of the US Congress and Sunday ser- like highly specialised production can and these choices, which begs the question: Is mons in Paris. A father in the Dominican do trigger unanticipated systemic crashes. efficiency a characteristic of simplified sys- Order preached that the “love of God is the tems or oversimplifying minds? Taylor System of our inner life.” However, THE FOUR ‘SPIES’ TO AVOID The fourth and final covert identity of ef- for Taylor, the high priest of efficiency, sci- Efficiency may be portrayed as a paragon of ficiency is that of a trap, enticing the mark entific management was bigger than time rational thought, but this can be a cover for with the idea of unquestioned goodness. and task-tracking. It was a “mental revo- its more duplicitous aspects. Understanding How, after all, could being more efficient be lution.” In reality, though, that revolution four covert identities may help in uncover- anything other than a positive thing? The faced resistance. Consider slacking on the ing this guise. simple answer is that numerical objectives production floor—or “soldiering,” as Tay- The first and the most familiar is when that are divorced from human concerns are lor termed it. When factory workers lolly- efficiency serves as a toy. In this aspect, effi- not innately beneficial. Indeed, the world is gagged, that meant revenue loss. But when ciency produces gains that make countless full of examples where the “efficient” solu- the companies following the Taylor Sys- conveniences possible, from live-streaming tion had monstrous consequences. tem tried to eliminate these unwanted idle to frozen lasagnas and express-delivered In Tinker Tailor Soldier Spy, le Carré times, pointing to accountability, employee Nordic socks. Each application is endless- wrote, “The more identities a man has, morale and burnout problems increased. ly—and separately—optimised for effi- the more they express the person they con- Efficiency in practice was not an unalloyed ciency, systematically tuning individual ceal.” The same is true for efficiency. To advantage. preferences into parameters. But if greater become nuanced and skilled in questioning In a society with countless efficiencies, efficiency merely produces the newest fad the toys, theories, traditions, and traps of no two are alike. In a recent analysis, man- rather than a material gain, we are right efficiency, we need to unmask our risky flir- ufacturing policy scholar Erica Fuchs and to question whether a benefit has been tations with it. That’s how we can engineer colleagues cited a mid-sized American com- achieved. efficiencies that don’t just make us better pany that struggled to produce nine mil- The second identity emerges when effi- off, but better. 7 lion masks during the initial stages of the ciency becomes a general theory. Over the COVID-19 pandemic. The chief hurdle was past century, the shopfloor concept has been Guru Madhavan is the Norman R. not in sourcing the core ingredient—melt- exported to the management of working Augustine Senior Scholar and senior blown polymer—but in sourcing the elastic hours. The typical 40-odd-hour workweek director of programs at the US National cord for the mask’s ear loops: The sole US with meetings, emails, calendar invites, Academy of Engineering. supplier of the elastic could not quickly teleconferencing, and action items is more @BioengineerGM 12

SHAASTRA 2021 May-Jun 14.indd 12 5/18/21 7:27 PM SHAASTRA 2021 May-Jun 14.indd 13 5/18/21 7:27 PM GUEST COLUMN THE JOY OF LEARNING SCIENCE To stoke young minds and light the spark of curiosity, India needs a ‘Tippe-Toppian revolution’ in education.

STMOOL / 123RF taneously turns upside-down and rotates on its stem, elic- RAMJI iting an Aah! from observers. RAGHAVAN Solving the physics of the phenomenon offers that rare Aha! moment, made special by the Ha-Ha! of play. A famous picture shows YING SICK IN BED, five-year-old Al- Nobel laureates Wolfgang bert Einstein was ignited by the gift – of Pauli and Niels Bohr demon- La magnetic compass – from his father. strating the Tippe Top in a It was perhaps “the gift of the century.” In moment of child-like curi- his 70s, Einstein said it was the magnetic osity. A Princeton professor compass that made him wonder if there was spent a whole night playing an invisible force behind everything in the with a Tippe Top that I had universe. gifted him – and on working Exposed to hands-on, counter-intuitive out the math behind its be- science experiments, young Pandurang of haviour. The top costs all of Mumbai described his epiphany as no lon- ten rupees. It demonstrates ger wanting to be a bicycle repairman like powerful learning on the his father, but of wanting “to be an inven- cheap, a talisman for Upside tor.” It costs little to spark curiosity and set Down thinking. Likewise, Vijaya, a village girl, movingly describes millions on the path of exploration. many of Agastya’s innova- the impact of learning with creative, hands- tions, including its creativity on science experiments: “I am not afraid to campus, award-winning mo- speak anymore.” from ‘textbook-bound’ to ‘hands-on’, and, bile science labs, labs-on-motorbikes and Inciting experiences that are counter-in- most critically, from ‘fear’ to ‘confidence’. Covid-inspired phygital home labs sparked tuitive, unexpected and well-timed can play The results of impact studies, developed by a lone instructor’s digital origami activ- an invaluable role in transforming an indi- with the help of IIM Bangalore and conduct- ity, resulted from constant experimenting vidual’s thinking, self-belief and worldview. ed with over 1 lakh students, have supported and questioning, top-down and bottom-up. Could such mesmeric learning experiences these aims. Working hands-on with 15 million un- be disseminated at scale to change a coun- India’s Golden Age was defined by cu- derprivileged children and thousands of try’s destiny? riosity, a trait that all of us are born with. government schoolteachers offers some im- Former Atomic Energy Commission Curiosity, paradoxically, is scarce in India. portant lessons: Chairman P.K. Iyengar once told me: “Ex- The reason can be traced to how we engage 4 Creative learning is not a luxury, but a posing a non-science graduate like you to with children. I recall an animated class in necessity for the underprivileged hands-on science experiments will make Jaipur. The children competed excitedly to 4 Getting learners to shift from ‘what to you see the world very differently.” answer the teacher’s questions. It was riv- think’ to ‘how to think’ is not difficult or eting – except that not a single child asked expensive THE SPARK OF CREATIVITY a question. I asked the children why that 4 Transformation at scale needs enabling In constructing a new vision for learning, was so, and a girl replied simply: “fear.” I environments that promote question- the founders of Agastya International left in despair, wondering why even if one ing, observing, experimenting, and the Foundation started not with facile answers implored children, they were afraid to ask pursuit of unusual connections but with searching questions such as: what questions. 4 Building an enabling environment re- is creativity, is creativity in your genes To my delight, the same instructor pro- quires skills different from those need- or an acquired skill, should creativity be duced a ‘miracle’ the following day. He ed to achieve individual excellence nurtured top-down (fill the glass with holy transformed his class into groups and as- 4 Individuals and organisations that water) or bottom-up (raise the level of the signed them a peer-to-peer ‘question game’, experiment and innovate have a ‘resil- ocean by a millimeter), and how might one which ended up producing scores of thrill- ience advantage’ over those that do not raise the speed limit of creativity of an en- ing questions. When people ask me “How tire nation? We agreed that questioning, can I spark curiosity in my child?” I ask Imagine a nation of a billion curious observing, engendering awareness, exper- the counter-question: “Have you asked your souls, tinkerers, creators, problem-solvers imenting and associating were ‘learnable child what questions she asked in school and grassroots innovators. India could be discovery skills’ critical to foster creativity today?” I am commonly met with a look of that nation if, and only if, it effects a radical and innovation, and raise productivity and surprise, if not guilt. change in its learning systems. India’s new prosperity. national education policy could catalyse a The mission to “spark curiosity (Aah!), LOW-COST LEARNING TOOL much-needed Tippe-Toppian revolution for nurture creativity (Aha!) and instill con- Fortunately, it costs little to spark curiosi- a more creative and resilient nation. 7 fidence (Ha-Ha!)” among underprivileged ty – the world’s most vital natural resource children and government schoolteachers – and set millions on the path to creative Social innovator and entrepreneur Ramji through experiential hands-on science exploration. The Tippe Top, for example, Raghavan is founder and Chairperson learning aims to trigger vital behavioural is a colourful, somewhat eccentric toy with of Agastya International Foundation. He shifts: from ‘yes’ to ‘why’, from ‘looking’ to a narrow stem and a round bottom. When serves as member of the Central Advisory ‘observing’, from ‘passivity’ to ‘exploration’, activated, it spins on its bottom and spon- Board of Education, Government of India. 14

SHAASTRA 2021 May-Jun 14.indd 14 5/18/21 7:27 PM Together... Shaping the Future of Electricity

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SHAASTRA 2021 May-Jun 14.indd 15 5/18/21 7:27 PM INDUSTRY

NAMAS BHOJANI

THE CHIPS ARE UP! After several false starts over the decades, the semiconductor industry in India awaits a new dawn – and a fabless future!

K.C. KRISHNADAS other for 4G and 5G infrastructure, both communications. Steradian Semiconduc- built using Taiwanese fabs. One of the tors developed radar transceiver chips for RINATH Sridharan, Shyam chips didn’t sell as well as had been hoped, the automotive market, a difficult industry Somayajula and Kishore Ganti but the company had been noticed by ven- to crack. SignalChip launched four prod- came to Bengaluru from the U.S. ture capitalists and industry veterans. ucts, including a chip for 4G, LTE and 5G in 2006 to set up a development In 2018, a Chinese private equity firm modems, in the past two years. centre for Silicon Labs. They picked up a majority stake in Aura, open- After a long lull, the fabless semicon- had advanced degrees in coming up a new market for the company. A ductor industry has seen a few start-ups, puter science and significant experience at series of Aura products for the Chinese including the likes of InCore Semicon- Ssenior engineering positions in prominent market followed in rapid succession. So ductors, Kalatronics Semiconductors and multinational companies abroad. As they far, it has designed 12 chips and shipped LightspeedAI Labs. Meanwhile, two major began work on the centre, they also started 20 million of them, and is on the way to Indian Institutes of Technology (IIT) had thinking about setting up their own venture. launching ten more this year. Within a few been developing their own chips. In 2019, They had studied in India for their under- years, Aura had gone from being a small IIT Bombay developed a processor, called graduate degrees, knew the semiconductor IP and services company to becoming one AJIT, with funding from the Ministry of industry well, and wanted to bring their ex- of the most watched semiconductor com- Electronics and Information Technology pertise to a home-grown venture. panies in India. “Once you have market (MeitY) and technical help from the pri- The three friends founded Aura Semi- and consumer access,” says Ganti, “the IC vate design automation firm Powai Labs. conductor in 2010. They had novel ideas definitions just keep flowing.” Last year, IIT Madras developed SHAKTI, about Integrated Circuit (IC) design, but an open-source processor fabricated at a they focussed on services and intellectual HEAPS OF CHIPS foundry in Chandigarh owned by the De- property (IP) in the early days of the com- Aura’s sudden change in fortunes has been partment of Space. Putting it all togeth- pany, spending most of their energy on accompanied by increased activity in a er, some industry observers now feel that building an engineering team and working few other companies, all Bengaluru-based, semiconductor industry in India is about towards their first round of funding. With- that have also launched their own chips – to turn a corner. in a few years, the company had a top-class even if not so spectacularly. Cirel Systems In reality, these are small steps for a engineering team. After they raised $6 mil- has shipped 50 million chips cumulatively country that seemed poised to become a big lion from WRVI Capital in 2016, the team in its eight-year history. Saankhya Labs player in the semiconductor industry a de- started thinking seriously about building launched two products: a software-defined cade ago, just before the time Aura was set products. Two years ago, Aura launched radio platform and another aimed at mo- up. By then India had seen two decades of its own ICs, one for mobile phones and the bile devices, broadcast TV and satellite semiconductor development in multination- 16

SHAASTRA 2021 May-Jun 14.indd 16 5/18/21 7:27 PM Saankhya, with its semiconductors for A fabless policy various applications, has in the works

proved that it is possible India’s fabless design industry could to create fabless get a boost with a national policy planned by MeitY to bring 50 fabless companies in India. firms together to launch 100 ICs in five years. The intended investment ular intervals after that, they never did. The is about `1,000 crore. global semiconductor industry had been go- The IESA is working to enable it ing through a difficult period in that decade. to support new and existing projects As semiconductor companies made chips at to be chosen based on the idea, tech- smaller and smaller dimensions, their capi- nology, commercial viability and the tal costs went up steeply. It was hard to form team for support at seed and growth Saankhya Labs CEO Parag Naik, a start-up and succeed in the business, even stages, according to Chairman Satya framed against a chip designed by if the founders had original ideas, because Gupta. IESA hopes to put together a his company. The company’s success the money needed to break into the mar- `4,000-crore fabless seed fund as suggests a fabless semiconductor ket was too high. A start-up could raise $20 well. industry has taken root. million and yet not have enough money to “The IESA initiative is welcome. bring its products to the market. The first utilisation of this funding Indian companies found it hard to thrive should be to change the mindset in this situation. Semiconductor design to enable product-like thinking and is a hard job, requiring domain expertise, activity,” said Manju Hegde, CEO of engineering skills – and quite some mon- Texas-based radar-on-chip start- ey. Although a pool of talented engineers up Uhnder. Hegde, an IIT Bombay had formed in India, the barriers to entry alumnus, previously co-founded chip to the international market were high for firms Celox Networks and AGEIA Indian entrepreneurs. Even fabless chip de- Technologies, which developed part sign start-ups, which required significantly of their chips in India, just as Uhnder lower investments to set up, did not form in now does. large numbers in the country. Things had A critical mass of Indian fabless in fact looked bleak for those who expected companies is now beginning to work high-quality companies to emerge from In- in AI and ML, communications and dia at regular intervals. However, by 2018, computing, and are designing so- the world market had begun to change, phisticated systems. Areas that need bringing optimism to the industry. strengthening are product conceptual- isation, architecture and post tape-out al research and development centres, which RIDING ON DATA, AI activities leading to volume production created a large pool of skilled engineers in The optimism was fuelled by two major and the business side of things. Bengaluru and other cities. Some of these changes: the rise of data centres, and Arti- Indian academia, on the other hand, engineers had started moving out of the ficial Intelligence (AI). As data centres in- has done well in analog and mixed-sig- multinational centres and setting up com- creased in number and sophistication, and nal. “If the two technical competencies panies early in the century. In 2007, the In- storage moved to the cloud, companies need- are combined with product marketing dian government had, in its semiconductor ed cloud-related chips in large numbers. The to create commercially viable global policy, mulled setting up a fab in India; the use of AI and Machine Learning (ML) in a products, we will do well,” says Gupta. Indian semiconductor industry seemed set number of industries also drove the develop- IESA plans to set up a Silicon Valley to take off sometime during the next decade. ment of AI-related chips by start-ups. chapter as a means of creating a free- Many start-ups in these sectors have way of exchange with the Indian semi- A FALSE DAWN raised significant funding and have high conductor ecosystem. It will cover It didn’t happen as expected, although there valuations. The most significant example design centres, fabless start-ups and were a few small successes. One of them is the Silicon-Valley-based SambaNova funding and, most importantly, will was Cosmic Circuits, a product company Systems, which builds platforms for run- develop a strong connect with semi- set up in 2005 by Ganapathy Subramaniam, ning cloud-based data centre applications, conductor leaders of Indian origin in an engineer from Texas Instruments (TI In- and has raised $1 billion since it was set up the Valley. Indian firms have reached dia). Cosmic was the first Indian company in 2017. It includes a $676 million series D out to senior people of Indian origin as to focus exclusively on products, and it de- funding from investors led by SoftBank, mentors and strategic advisors. 7 veloped analog and mixed-signal chips for at a valuation of $5 billion. In 2019, Intel analog-to-digital converters, temperature acquired the three-year-old Israeli AI chip sensors, audio codecs and so on. When Cos- start-up Habana Labs for $2 billion. The semiconductor start-ups have been raising mic was acquired in 2013 by Cadence Design U.K.-based Graphcore, set up in 2016, has large amounts of money. In April 2021, the Systems for $70 million, the Indian semicon- so far raised $682 million and was valued Chinese chipset firm Unisoc raised $814.6 ductor industry saw a rare acquisition. The at $2.8 billion in December 2020 when it million from a team of investors. only previous acquisition of significance raised $222 million. China is also the world’s largest and was of Armedia, a digital video IC firm, by Several other AI semiconductor start-ups fastest-growing semiconductor market. Broadcom in 1999 for $67 million. have raised significant funding or been ac- According to the Semiconductor Industry Although Indian observers expected quired at high valuations. High valuations Association, sales in the Chinese market start-ups and acquisitions to happen at reg- are especially common in China, where were $151.1 billion in 2020, roughly 36% of 17

SHAASTRA 2021 May-Jun 14.indd 17 5/18/21 7:27 PM INDUSTRY

Focussing on chip design India’s semiconductor industry is expand- portfolio start-up developing IP for ICs, ing incubation and mentoring initiatives to looks to SFAL for inexpensive access to spur fabless design. The most significant prohibitively priced design tools. Such of them is the Semiconductor Fabless tools are important and, being expensive, Accelerator Lab (SFAL), Bengaluru, head- difficult to access for start-ups. ed by Muthukrishnan Chinnasamy, who The Fabless Chip Design Incubator worked at TI India and has founded chip (FabCI) at IIT Hyderabad, an incuba- design firms. tion initiative that looks to create an “There are some 50,000 engineers in ecosystem for chip design start-ups, chip design in India. Harnessing their includes Lemon Flip Solutions, which skills, we can build our own innovative is developing ICs for military and other designs,” Chinnasamy said. defence applications. FabCI helps with SFAL, funded by the Karnataka gov- angel funding, design tools, prototyping ernment to boost fabless start-ups, has and characterisation facilities, mentoring chosen 12 firms for incubation and men- and foundry access. toring and invested in four of them. Port- Other similar though private initiatives folio firms include Calligo Technologies, are the Semiconductor Startup Incubation focussed on Big Data and AI; Kalatronics and Acceleration Program launched by Semiconductors, which is into IP solutions Dutch chip firm NXP Semiconductors, in for faster interconnect speeds; Morphing collaboration with MeitY and FabCI; and Machines, with its many-core, massively the Hubballi-based KLE Technological parallel, runtime reconfigurable embed- University’s Centre for Technology Inno- ded ICs; and LightspeedAI Labs. vation and Entrepreneurship, with Semi- For example, Prasad Panchangam, Ksha Semiconductors being a portfolio founder, Saigeware Technologies, a SFAL start-up. 7

the global market of $439 billion. In con- sold 20 million chips while being a division trast, the Indian market was just $21 bil- of Cosmic, and has since sold another 30 lion in 2019. million as a separate company. Faced with such a small domestic mar- Cirel’s success is partly due to its having ket, Indian companies struggled to design chosen a domain, the stylus, where it has products. A semiconductor ecosystem did become one of the world’s leading players. conductors. These companies, and indeed not develop in the country except in isolat- Cirel has had a sudden increase in business almost every fabless design firm in India, ed pieces. In its early years, Aura did not in the last one year, and remains one of the were either founded by former employees find it easy to conceive products for specific few – if not the only – company in the coun- of TI India or have core teams from it. markets. Once it raised funding, investors try that can make and ship chips in large Saankhya has several engineers who have sensitised the company to the potential of volumes. “Though Cirel’s IC is small, it spent long periods in TI. the Chinese market and the company grew shows it is possible to create fabless compa- “In the late 1980s and ’90s, the TI leadership rapidly. However, it grew on a foundation nies in India,” says Subramaniam, also the took pride in doing more and more complex built in the first half of its life. It had built company’s Chairman. chips from India. This, coupled with the fact a large team of skilled chip designers that A few other companies too have demon- that in those days they attracted very good a development centre in China supple- strated that. Saankhya, with its wireless tech- talent, has led to TI individuals taking on not mented. “Aura creates chips as good as any nology and semiconductors for applications only entrepreneurial roles but senior roles American company,” says Subramaniam, ranging from rural broadband to satellite in many other semiconductor companies,” now a partner in WRVI Capital, which first communication, has solutions for 5G, includ- says Cirel Chief Executive Officer Sumeet invested in Aura. ing 5G broadcast. Other products include Mathur, who himself worked in TI India. Change happened slowly in the Indian radio access network analytics support and Indicatively, Sankalp Semiconductor, a fa- market over two decades as companies a “dynamic cell edge detection” that helps bless design firm that was acquired by HCL learned to utilise their design expertise for interference management and modulate Technologies, was started up by Vivek Pawar, the overseas market. Now some entrepre- emitted power, techniques that improve both who had worked for years at TI India. So com- neurs are trying harder than ever to crack capacity and power consumption. One of its pletely does TI India lord over the country’s the overseas market. “India will open up as previous chips, Pruthvi-3, is a game-changer fabless ecosystem that the Bengaluru-based a market at some point, but it may be too for the telecom and broadcasting industries fabless semiconductor consultancy EmuPro, late to enter it then,” says Ganti. by enabling convergence of the two. with half a dozen clients, is headed by Anoop Steradian, which has assembled a top- Dutta, himself an ex-TI India staffer. DESIGN EXPERTISE notch engineering team, is into cutting-edge Even beyond founders with roots trace- India has over 50,000 designers working imaging radar ICs fabricated at overseas able to TI India, new companies are still be- for multinational firms, and they provide foundries, and similar products aimed at ing formed, although at a slow pace, which a big pool of expertise for those who want the global automotive and industrial mar- has become a feature of India’s semicon- to make sophisticated products. kets and applications ranging from traffic ductor industry. Some of these companies Cirel Systems, for example, has been able monitoring to indoor sensing. are indeed developing AI chips, the current to break through to the overseas markets trend in the industry around the world. rapidly in the past two years. Originally THE NETWORK EFFECT LightspeedAI Labs is developing an op- a business unit of Cosmic Circuits, it was The stories of Cosmic, Saankhya and toelectronic chip that uses light for com- spun off as a separate company after Cos- Steradian show how multinational cen- puting. Alpha IC, a company set up in 2016, mic was acquired by Cadence. Cirel had tres spawn high tech companies in semi- uses principles of AI for edge computing, a 18

SHAASTRA 2021 May-Jun 14.indd 18 5/18/21 7:27 PM NAMAS BHOJANI

(Above) Cirel Systems CEO Sumeet Mathur, High-end fabs are too wields the stylus, embedded with a Cirel- costly to build in India. designed chip, which has made it a global But there may be scope to player. (Left) IESA Chairman Satya Gupta. business consulting firm Frost & Sullivan. It build fabs making low-end put the overall consumption of electronics chips in high volumes. components at $31 billion, with two-thirds of it accounted for by semiconductors. method of computing where the data is pro- “India does not have an indigenous orig- cessed by the device and not the cloud, a rap- inal equipment manufacturing ecosystem idly rising market. InCore Semiconductors, that can source our chips,” said Saankhya a start-up with roots in IIT Madras, is also CEO Parag Naik. developing IP in AI. “India has been left behind in the electronics and semiconductor product market. It is A FABLESS FUTURE imperative that we pursue both electronic Although setting up a fab in India becomes products and semiconductor development increasingly difficult as technology advanc- vigorously,” said Ravi Thummarukudy, es, costs increase and little original equip- CEO, Mobiveil, California, and co-founder ment manufacturing continues, many ob- of chip design solutions firm GDA Technol- servers feel that developing a large fabless ogies, later acquired by L&T Infotech. semiconductor industry is not too difficult Electronics production currently con- now. “That successful fabless product compa- tributes 3.3% to the Indian economy and nies can be built without having indigenous devices are now being manufactured that is expected to grow to $320 billion by 2025. fabs has been demonstrated by Qualcomm require small chips in them, such as smart However, new and additional measures give and Broadcom in the U.S.,” says Satya Gupta, cards and highway tags. These may not be it the potential to reach as much as $410 bil- Chairman, India Electronics and Semicon- cutting-edge technology but have good busi- lion, or 8.2% of India’s targeted economy ductor Association (IESA). In India, the re- ness potential. India is yet to move in this size of $5 trillion, IESA said. cent successes of Cirel, Aura and Saankhya – direction, but observers believe a long-term With semiconductor content in elec- although modest by international standards plan can trigger rapid change. tronics rising and the use of electronics – suggest a fabless semiconductor industry For example, there is a good home market itself also on the rise, Indian fabless de- has taken root and holds potential. for semiconductors; semiconductor con- sign firms cannot complain of the lack of Although high-end fabs are too expensive sumption in India was about $21 billion in a home market anymore. A national elec- to build in India, there may be an opportuni- 2019, growing at the rate of 15.1 per cent, ac- tronics mission is also believed to be in the ty for building fabs that make low-end chips cording to IESA’s Electronic System Design works; perhaps, fabless design can get a in high volumes. A large number of new and Manufacturing 2020 report done with boost from it. 7 19

SHAASTRA 2021 May-Jun 14.indd 19 5/18/21 7:27 PM COVER STORY

ALEXLMX /123RF 20

SHAASTRA 2021 May-Jun 14.indd 20 5/18/21 7:27 PM INDIAN BIOLOGISTS ARE WORKING TO UNDERSTAND THE CORONAVIRUS BETTER, AND ARE HOPING TO USE THAT KNOWLEDGE TO DEVELOP BETTER VACCINES FOR THE FUTURE.

ROMASTUDIO/123RF 2021/00 bimonthly 21

SHAASTRA 2021 May-Jun 14.indd 21 5/18/21 7:27 PM COVER STORY

HARI PULAKKAT COVID AS CATALYST of technological advances that happened India, with a compara- over the past decade helped scientists to HE CRYO ELECTRON Mi- tively medium-sized sci- rapidly sequence the virus, look at it from croscope (Cryo-EM) is rarely entific ecosystem, has close quarters, and get vaccines ready very seen by the public as a weapon not been in this game quickly. However, the fight against COVID to fight the COVID-19 pandem- except in small ways. The and other viruses will go on for a long time. ic. Costing nearly `50 crore COVID pandemic, how- So scientists are using even deeper science and requiring an additional ever, has induced some and more advanced technology to develop `30 crore for infrastructure, it is among scientists to adapt their vaccines that will make their way into clin- Tthe most coveted pieces of equipment work to future vaccines. ics over the next few years. in modern biology laboratories. Its high While it may take some Cryo-EM is one of the most recent price meant that Indian laboratories have time for their research and significant of these developments. been slow to get the machine. The Nation- to result in commercial Next-generation sequencing is another al Centre for Biological Sciences (NCBS) products, they are lay- piece of technology that has completely in Bengaluru got the first state-of-the-art ing the groundwork for changed the approaches to viruses and Cryo-EM in the country, but several more next-generation vaccines vaccine discovery. Although developed are on the way now: at the Indian Insti- in the country. more than a decade ago – commercial tute of Science (IISc) in Bengaluru, the There is never a good systems have been available since 2005 Centre for Cellular and Molecular Biology time for a pandemic, but – next-generation or massive parallel se- (CCMB) in Hyderabad, and at IITs in Del- the year 2020 was perhaps quencing has been gaining in power over hi, Chennai and Mumbai. a better time than any the last decade and has been used in inge- At IIT Delhi, virologist Manidipa Baner- other to deal with nious ways to figure out the stability of jee will get her new machine later in the one. A number proteins, an important piece of informa- year: she was supposed to have got it last tion while designing antibodies against year, but it’s been delayed by the viruses. The development of techniques to pandemic. IIT Delhi has an make mRNA vaccines was another recent older machine but the new advance, and so are methods to make ad- one is more powerful and juvants that help vaccines perform their lets scientists see proteins tasks more efficiently. There are many oth- from up close, with a clear er precise techniques that are now being view of where smaller mole- tailored to study viruses and how they cules attach to them. For Baner- attack the host. jee, the Cryo-EM is an invaluable Banerjee’s primary interest is tool to see how antibodies dock to vi- on how viruses assemble them- ruses. By watching how antibodies and vi- selves and gain access to the ruses lock on to each other, scientists can host cellular machinery, determine vulnerable spots in the virus. a useful piece of knowl- A state-of-the-art Cryo-EM operates edge in designing fool- at 300 kilovolts (kV). Banerjee’s old- proof vaccines. At er machine works at 200 kV, but IISc, structural it was good enough for her to do some work on the SARS- CoV-2 virus. Using it along with a more modern one at the national Cryo-EM facility at the NCBS, she has developed a vaccine candidate and a platform technology. “The chance of another pandemic is high,” says Baner- jee. “We should have multiple kinds of technologies so that we are ready the next time something happens.” In major laboratories around the world, scientists are using advanced equipment In major and deep science to understand the struc- laboratories ture and behaviour of the SARS-CoV-2 virus. Over the next few years, they expect around the world, this improved understanding to result in scientists are using better vaccines that can be developed rapidly when a need arises. These vaccines advanced equipment will be more effective in low doses, can be transported easily and cheaply, and will and deep science to work against a larger number of viral understand the mutations. The holy grail of vaccine research, though, is still far away: a vaccine structure and developed within weeks or days of a pandemic, which can work against any mutat- behaviour of the ed form of the virus. SARS-CoV-2 virus. 22

SHAASTRA 2021 May-Jun 14.indd 22 5/18/21 7:27 PM SHAASTRA 2021 May-Jun 14.indd 23 5/18/21 7:27 PM COVER STORY

DILEEP PRAKASH

In her IIT Delhi laboratory, virologist Manidipa Banerjee used cutting-edge a method known as x-ray crystallography, vide more generalised immunity, includ- Cryo-EM technology to develop a vaccine they had to get the protein to crystallise. ing against new mutated forms of viruses. candidate for the SARS-CoV-2 virus. This is often hard – and, in some cases, im- There are several methods to provide possible. Cryo-EM got around this problem generalised immunity. One is to have biologist Raghavan Varadarajan at the Mo- by rapidly freezing the sample, letting biol- multiple proteins from the viral surface, lecular Biophysics Unit (MBU) works on ogists see proteins at high resolution. so that at least one of them will work protein structure and stability; this knowl- Technologies for the Cryo-EM had been against mutated forms. A second approach edge, too, is invaluable in designing stable under development for two decades, but is to look at parts of the virus that do not proteins that can work as vaccines. At IIT change during mutations, and then use Kanpur, Dibyendu Kumar Das studies how that part to develop a vaccine. It is a hard the virus changes conformation – the way problem to solve, as the unchanging parts its proteins are arranged – before entering There are 17 varieties of are usually buried deep inside – and so not the host cell, and how this conformational the influenza virus and easily accessible to the immune system. change is important for breaking into the Both these methods are being tried now host. only four are circulating for COVID-19. At the Centre for BioSystems Science Banerjee uses the first approach of using and Engineering at IISc, Siddharth Jhun- in the human population. multiple particles on the viral surface. She jhunwala works on engineering immune But the others have the was on the verge of starting animal trials responses to viruses and other invaders. with one such vaccine, consisting of four By studying how materials interact with potential to spread – with protein particles, in collaboration with the the immune system, he could develop ad- much higher fatality rates Translational Health Science and Tech- juvants that improve the efficacy of vac- nology Institute in Delhi, when the second cines. After the COVID-19 pandemic, all than SARS-CoV-2. wave of the pandemic hit the country. these scientists redirected their research At IISc, Varadarajan is trying to use the towards developing vaccines at some time second approach, looking for proteins that in the future. the technique became mainstream only do not mutate easily, to develop vaccines early in the last decade. Virologists were for both COVID-19 and influenza. Such a THE CRYO-EM EDGE among the first to use this technique as combination vaccine may be necessary The Cryo-EM won its developers a Nobel it let them see the antibody and the virus sometime in the future. Epidemiologists Prize in 2017. One of them, Richard Hen- attached together. The microscope gave consider respiratory viruses as among the derson of the Molecular Research Labora- them a tool to look at different parts of the biggest threat to public health, and corona- tory at Cambridge, was closely involved in virus and see which protein can trigger an viruses and influenza viruses are among setting up India’s national Cryo-EM facili- immune response, and how antibodies at- the most threatening respiratory viruses. ty at NCBS in 2017; his student Vinoth Ku- tach themselves to the protein on the virus The influenza virus exists in 17 varieties, mar moved to NCBS as part of the ‘pack- surface. Such techniques were used by vac- but only four are circulating in the human age’. The Cryo-EM solved a major problem cine makers in the early days of the pan- population at the moment. Reservoirs ex- that structural biologists faced: to figure demic to develop vaccines. Now they are ist for the remaining varieties, and they out the structure of a protein using x-rays, being used to develop vaccines that pro- have the potential to spread in humans 24

SHAASTRA 2021 May-Jun 14.indd 24 5/18/21 7:27 PM NAMAS BHOJANI The holy grail of vaccine research, though, is still far away: a vaccine developed within weeks or days of a pandemic, which can work against any mutated form of the virus.

without any warning with much higher fatality rates than SARS-CoV-2. Varadarajan does not use a Cryo-EM to find the protein structure. Instead, he looks for mutations in the amino acid sequence of the virus, especially for the so-called correlated mutations, which are changes in two amino acids at the same place in two different proteins. By building a library of correlated mutations and comparing them, scientists are able to figure out the configurations of proteins and predict the structure. Alphabet subsidiary DeepMind uses correlated mutations to predict protein structures. In 2012, Varadarajan was among the first few biologists in the world to use rapid sequencing to judge mutation rates and analyse these mutations to figure out the structure of proteins. Now he uses this technique for vaccine development. When biologists have a single protein, Cryo-EM remains the most powerful technique that biologists can use. Varadarajan At IISc, Raghavan Varadarajan is does not need this technique so much be- ologists like him hope to develop a single looking for proteins that do not mutate cause he looks at the structures of a large vaccine that can work against all forms of easily in order to develop vaccines for both collection of proteins. His aim is to figure influenza. It is one of the hardest problems COVID-19 and influenza. out mutations in the virus that result in for virologists to crack. stable proteins. In other words, his interest For a coronavirus, the lack of stability of In 2017, Das moved to Tufts University is not in a specific structure but in finding surface proteins may be part of a strategy to work with Munro on the HIV virus as methods to stabilise a specific sequence of to penetrate the host membrane. For exam- a post-doctoral scholar. Das and Munro amino acids. Proteins on the surface of vi- ple, many viruses, including SARS-CoV-2, showed in 2018 that the HIV envelope was ruses are stable only for short periods, and go through a change in the conformation intrinsically dynamic. so it is not easy to use them for generating of proteins in their surface just before en- Das moved to IIT Kanpur in 2019 to antibodies. Which is why all the attention tering the host cell. Cryo-EM has provided start his own laboratory, where he stud- of vaccine developers is focussed on the good images of conformations before and ied the Ebola virus and SARS-CoV-1 virus. stable spike protein. after the entry into the cell, but they are When the COVID-19 pandemic started, static images. Cryo-EM uses frozen sam- he switched to the SARS-CoV-2 virus. Its STABILISING THE PROTEIN ples, and so cannot watch the spike protein structure is not too different from that of Molecules other than the spike protein go through the conformational change. This the older SARS virus. Using FRET, he now could be developed as vaccines if scien- is done through another technique called tracks the conformational changes of the tists could find a way of stabilising them. Fluorescence Resonance Energy Transfer spike protein in the SARS-CoV-2 virus as Stabilising the protein is also important in (FRET), which Das uses at IIT Kanpur in it enters the cell. Once the intermediate preventing the virus protein in changing combination with powerful microscopes. forms of the spike protein are mapped out, conformation, a process that is important FRET uses energy transfer between scientists can look for more vulnerable for it to move inside the cell. Varadarajan two fluorophores – compounds that can spots on the protein, apart from what are is using his knowledge of protein stabili- emit light when excited – to measure the obvious before the change in conformation. ty to develop a combination vaccine for distance between them. Till early this It is a big jump in understanding the COVID-19 and influenza (See‘This vaccine century, it had been used only to measure virus. “It is one thing to see that a huge can take the heat’, Page 26). “If the virus average distances in collections of mole- structural change has happened,” says has a large and stable protein, vaccines cules. Single-molecule FRET used similar Das, “and quite another to map out the are more likely to get a better antibody re- principles to measure distances between trajectory.” Once the intermediate stages sponse,” says Varadarajan. parts of a large molecule like proteins. In of the change are clear, scientists will have By using new, stabilised proteins on the 2014, James Munro at the Tufts Universi- more sites on the spike protein to exploit. viral surface, he hopes to develop vaccines ty School of Medicine in the US used it to It may be that some of them are more re- that can work in mutated forms of the understand the conformational changes sistant to mutations and so more vulnera- virus. One day, using such principles, bi- of HIV protein as it entered the host cell. ble to vaccines. 7 25

SHAASTRA 2021 May-Jun 14.indd 25 5/18/21 7:27 PM COVER STORY

PHOTOS: NAMAS BHOJANI

Mynvax founders Gautham Nadig (left) and Raghavan Varadarajan at the IISc campus where their start-up was incubated.

THIS VACCINE CAN TAKE THE HEAT

The Mynvax vaccine But the alarming virulence and infectiv- ments of viral proteins to elicit an im- ity of the SARS-CoV-2 virus, which shut mune response in the human body. is particularly suited down economies around the world and Conventionally, scientists have used for Indian conditions: led to a high number of fatalities, forced a either a dead/attenuated virus, or an en- compelling change in priorities, virtually tire viral protein, as a vaccine. However, it is stable at high overnight, for Mynvax scientists. when researchers opt to use only a small temperatures, which A scramble began worldwide to develop fragment of the viral protein, they must a vaccine to save lives and protect humans understand the proteins of the virus well eliminates the need for a from arguably the most serious and most enough to be able to pick a region that can cold chain during transit. widespread public health hazard in over induce an optimal immune response in a century. And given their work in recom- humans. binant vaccine development, Mynvax re- For the COVID-19 vaccine, the Mynvax MANUPRIYA searchers were thrown into the frontline team identified a small strand (of 200 ami- of that life-saving quest. no acids) of the receptor-binding domain N JANUARY 2020, when COVID-19 At the urging of the Bill and Melinda (RBD) of the spike protein of SARS-CoV-2 had not yet begun to make grim news Gates Foundation, which reached out to as the initial vaccine candidate. The team’s – in India and around the world – re- Varadarajan in late January 2020, scien- previous work with the influenza virus searchers at Mynvax, a biotech start- tists at Mynvax doubled down on the work and its experience in protein engineering up incubated at the Indian Institute of to develop a COVID-19 vaccine. “They had helped it zero in on the receptor-binding IScience (IISc), Bengaluru, were immersed visited us a short while earlier, were fa- domain as the region capable of producing in work on vaccines for influenza and HIV. miliar with our work, and gave us a small an immune response. For the company – which had been amount of funding to start working on a This protein fragment then had to be founded in 2017 by Gautham Nadig, a bio- vaccine for COVID-19,” said Varadarajan. sequenced, and several copies of the frag- tech entrepreneur, and Raghavan Varada- ment made, so that it could be tested. To- rajan, a professor at IISc’s Molecular FRAGMENTS OF A VIRAL PROTEIN wards the end of March 2020, the protein Biophysics Unit – it was bread-and-butter Mynvax scientists’ approach to vaccine de- fragments were ready for the first round work, for which it had secured interna- velopment relies heavily on the research- of animal testing. But by then, COVID-19 tional recognition, including from the Bill ers’ understanding of protein structure. had acquired pandemic proportions and and Melinda Gates Foundation. Their vaccines typically use small frag- had triggered widespread panic, in India 26

SHAASTRA 2021 May-Jun 14.indd 26 5/18/21 7:27 PM If the COVID-19 virus olubilising the vaccine for the healthcare The Mynvax team is in the process of worker at the point of vaccination, the ad- conducting experiments to check the ef- mutates, the efficacy vantages of doing this are “far greater,” he ficacy of its vaccine against the mutant added. version of SARS-CoV-2, which was first de- of the Mynvax vaccine tected in the UK. “We don’t know for sure will be tested. But its WHAT IF THE VIRUS MUTATES what the outcome of these experiments Mynvax uses a “novel approach” to design will be. However, I will say that there is a founders believe they a COVID-19 vaccine, said T Jacob John, a good chance it will work,” said Varadara- are better placed to clinical virologist and former professor jan. Eventually, as more mutations accu- at the Christian Medical College, Vellore. mulate in the virus, an alteration in the respond quickly. “And although its potential is very high, a vaccine may be required. few cautions and caveats may be in order. Varadarajan compares this to the influ- For instance, against a highly mutating enza vaccines that are modified on a yearly and around the world. Schools and col- coronavirus, will this narrow target stand basis. Each year, the World Health Organi- leges had shut down, and offices were en- the test of time with emerging virus vari- zation (WHO) predicts the mutations that couraging employees to work from home. ants with mutations in the spike protein are likely to happen in the influenza virus On March 23, 2020, on the eve of the first and even the receptor-binding domain?” and provides recommendations on the nationwide lockdown in India, Mynvax re- he wondered. nature of the components that that year’s searchers put their protein fragments up By December 2020, the first mutant influenza vaccine should contain. The vac- for trial in mice. variant of SARS-CoV-2, first identified in cine manufacturers then modify the vac- Once the lockdown took effect, many re- the United Kingdom, had already been cine based on WHO’s recommendations. search scholars at the Mynvax lab had to recorded from India. Given that sobering “The mutation rate of the coronavirus is a head back home. It was quite a challenge reality, the question of whether the Myn- little less than that of the influenza virus. to conduct animal testing experiments vax vaccine will be effective against the So, we don’t expect that there will have and to collect data. Nevertheless, by April new strain is a vital one. As the virus accu- to be annual updation of the vaccine, but 2020, the first set of data on the efficacy of mulates more mutations, will this vaccine only time will tell,” said Varadarajan. the vaccine candidate was available; the perhaps prove ineffective? results were encouraging. Nadig agrees that as the virus mutates, THE ROAD AHEAD the vaccine’s efficacy might be affected. But, Despite its initial success in vaccine de- STABLE AND HEAT TOLERANT as he points out, the answer to this problem velopment, Mynvax has run into financial Several follow-up tests and studies later, lies in Mynvax’s unique approach to vac- challenges. Without access to adequate researchers concluded that the fragment cine development. “Our platform allows us funds, it is not possible for it to conduct (of 200-amino acids long) of the recep- to do rapid changes. It is going to take lon- safety studies and trials. The company has tor-binding domain of SARS-CoV-2 pro- ger for other types of vaccines to change. raised some funds from its investors, but it duced an effective immune response in Therefore, we will be fast to respond to any needs more to go further. It is also expect- mice and guinea pigs, was stable, and was mutation in the virus,” he said. ing some government grants, but there is surprisingly heat-tolerant. In the powder not much clarity on precisely when the form, it could tolerate temperatures as grant money will come through. high as 100°C, and was stable for over four In the powder form, the “Vaccine development is a risky propo- weeks at 37°C. They published their ini- Mynvax vaccine could sition, given that we don’t know what the tial findings in the Journal of Biological vaccine landscape will be in the future,” Chemistry. tolerate temperatures said Varadarajan. “Therefore, government Vaccines like that of Mynvax, which use funding is required to take this forward. a small fragment of a viral protein, are as high as 100°C, and The whole process needs to be de-risked,” called subunit vaccines. Globally, over 200 was stable for over four he added. vaccine candidates are in different stages “If we are able to secure adequate fund- of clinical or pre-clinical development. Of weeks at 37°C. ing, we should be able to start our clinical these, 20 are subunit vaccines. However, trials in ten months,” said Nadig. none of them have been reported as being The shortage of funds has slowed down stable at high temperature, so far. Neither progress at Mynvax, for sure, but it has se- have any of the seven vaccine candidates cured a lifeline of sorts. The company has in different stages of testing or rollout in entered into an agreement with a large India been reported as being stable at high vaccine manufacturer, which can help it temperatures. produce the vaccine at scale, so that it can This is especially important for India as initiate the trials. (Since the agreement is a high temperature-tolerant vaccine elim- bound by confidentiality, the researchers inates the requirement for a cold-chain were unwilling to share the name of the during transit. vaccine manufacturer.) Additionally, the In particular, “if the vaccine can lessons learnt in translating the labora- be transported in the powder tory research into a market-ready COVID form and resolubilised at the vaccine will also prove useful for the com- point of vaccination, it can pany’s influenza vaccine programme. save an enormous amount “When the HIV pandemic hit, re- of money – and the worry search in Immunology flourished. about whether the cold With the SARS-CoV-2 pandemic, vac- chain was maintained cinology research is flourishing. My- throughout the transit,” nvax’s work is an excellent example said Nadig. Though trans- of that,” said John. “This research porting in the powder form must certainly be encouraged and fi- does add an extra task of res- nancially supported,” he added. 7 27

SHAASTRA 2021 May-Jun 14.indd 27 5/18/21 7:27 PM COVER STORY MESSENGERS ON A LIF E-SAVING MISSION PHOTOS: JIGNESH MISTRY Two scientists, across continents, collaborated to bring the mRNA vaccine to India. The technology, adapted for COVID-19 times, could open up new opportunities to treat other killer diseases.

HARI PULAKKAT

TEVE REED first heard about Sanjay Singh more than a decade ago, when he went to the Na- tional Institute of Health (NIH) in the U.S., searching for people Swith expertise in manufacturing in India. Gennova CEO Dr Sanjay Singh. The HDT-Gennova partnership, which brought mRNA Reed, an immunologist and a microbiolo- technology to India in the nick of time, could transform the treatment of diseases. gist, was interested in tropical infectious diseases, and had been working on devel- the immune system mounting a response oping vaccines against leprosy and leish- Traditional vaccines against the vaccine itself. The solution was maniasis. He had expertise in vaccine adju- require large facilities found more than a decade later by Kariko vants, a closely guarded technology in the and her colleague Drew Weissman. They pharmaceutical industry. He had worked for culturing micro- tweaked the part of the mRNA that was at the NIH himself and wanted a business alerting the immune system and devel- partner with matching interests and some organisms or cells; oped a way of getting mRNA into the cells. expertise in manufacturing. “(Singh) was mRNA vaccines can be With this crucial breakthrough, mRNA a famous guy in NIH,” says Reed. “I wanted technology was ready to be developed as a someone to make things in India.” made in a small facility, therapy for a number of diseases. A major Sanjay Singh had worked at the NIH in and are easy to tweak for landmark came in 2012 with the founding Washington, D.C., for six years before he of Moderna in Boston as a vaccine com- decided to return to India in 2006. He had emerging mutations. pany. In 2013, Kariko joined a German done his PhD on malaria biochemistry immunotherapy start-up called BioNTech at the Central Drug Research Institute Reed is now trying to do clinical trials and helped the company’s journey towards (CDRI) in Lucknow, and had worked on in South Korea, China, and some African mRNA technology. mRNA vaccines were recombinant DNA technology at the Inter- countries for the HDT-301 vaccine. In April under development in BioNTech and Mod- national Centre for Genetic Engineering this year, Gennova started clinical trials erna when COVID-19 struck. A serious and Biotechnology (ICGEB) in Delhi be- for a modified product, called HGC019, pro- pandemic was a good opportunity to try a fore moving to the NIH. He had returned viding the country with a potential tool to new technology. BioNTech formed a part- to Pune to set up a company called Genno- control the pandemic in the long term: an nership with Pfizer, and Moderna went va as a subsidiary of the pharmaceutical inexpensive vaccine that can be quickly alone. Both vaccines were launched in company Emcure. Gennova had started tweaked, manufactured, and then distrib- 2020. It was a small first step for the world. its business by making drugs for cardio- uted rapidly around the country. The busi- Even before the product was launched, vascular diseases, but Singh had retained nesses of Reed and Singh had converged the drawbacks of the mRNA vaccine were his original interest in malaria and other unexpectedly to their original interests. evident. Messenger RNA degrades very tropical diseases. HDT Bio had generated the initial discov- rapidly and is therefore difficult to store A decade ago, after Reed called Singh, ery, and Gennova had improved the prod- and transport. The vaccine of Pfizer-BioN- their interests converged quickly in a busi- uct and the manufacturing technology. Tech is stored at minus 70º Celsius, which ness partnership. In 2019, Reed co-founded a is difficult to maintain in most countries. company called HDT Bio in Seattle for devel- A RADICAL IDEA On the other hand, the Moderna vaccine oping messenger RNA (mRNA) technology The idea of using mRNA for vaccines was can be stored at between 2º and 8º Celsius for cancer treatment. When the COVID-19 born in the early 1990s. Katalin Kariko, a for a month, a substantial improvement pandemic hit China, Reed immediately biologist at the University of Pennsylva- over the Pfizer vaccine. HDT-301 can be started tweaking the technology to develop nia, had made the first grant application stored as a liquid for two months at minus mRNA vaccines against the virus. Singh, in 1990 to develop the technology. Howev- 20º Celsius, but Gennova has improved it sensing that the battle against the pandemic er, it was too radical an idea for funding for storage between 2º and 8º Celsius for would be long and hard, approached the De- agencies, and no one was willing to fund two months. The original HDT vaccine partment of Biotechnology (DBT) for seed it, primarily because there was no way can also be dried as a powder and stored at money to develop an mRNA vaccine. of injecting mRNA into the body without room temperature for long periods. 28

SHAASTRA 2021 May-Jun 14.indd 28 5/18/21 7:27 PM MESSENGERS ON A LIF E-SAVING MISSION The mechanics of mRNA

Making a protein is a bit like making a dish using a recipe. And yet it is different from cooking in that the recipe is stored safely some- where and cannot be accessed by the chef directly. A messenger, called messenger RNA (mRNA), carries the information to make the protein – the sequence of amino acids – from the nucleus of the cell to the cytoplasm where proteins are made. Once the protein is made, the mRNA degrades. This elegant machinery makes sure that the blueprint for protein synthesis is not tampered with, and can be passed on from generation to generation without change, other than mutations that happen occasionally. In principle, it also gives scientists a method to make easily any protein that the body needs. Make an mRNA Gennova has built up a team of over 100 people for drug discovery and development. and put it inside the cell, and you could coax it to make the corre- Gennova has made some important sponding protein. THE UPSIDE changes to the original HDT-301 vaccine. In the last decade, biologists In spite of the storage difficulties, mRNA HDT had made the vaccine in two vials, one learned to synthesise mRNA of vaccines bring substantial benefits. For the dried mRNA and the other a substance any sequence in the laboratory one thing, they are easy to make and tweak. called a diluent, whose function is to recon- and developed methods to carry Traditional vaccines require large facili- stitute the vaccine for clinical use. Genno- it safely inside the cell. It is now ties for culturing micro-organisms or cells, va’s HGC019 is made in one vial. The dilu- relatively easy to make mRNA while mRNA vaccines can be made in a ent has a lipid-based nanoparticle emulsion in the laboratory but not so small facility. Since mRNA is synthetic, (LION) that is being tested for the first time, easy to carry it safely inside the there is no risk of contamination from live and so Gennova had to do separate animal cell without degradation. Since cells or viruses or bacteria. The mRNA vac- trials for LION and the vaccine. Over the mRNA degrades easily, it has to cine can be made very quickly, and it can next few months, the speed of its progress be attached to a larger molecule also be tweaked for emerging mutations will depend on how closely the results or wrapped inside a vesicle for rapidly. “The technology is so advanced match that of the other mRNA vaccines. delivery. It is also important that that you can start in the morning, and by The HDT-Gennova partnership brought the immune system does not rec- evening your vaccine is ready,” says Singh. mRNA technology into the country in the ognise mRNA as an intruder and If scientists spot a mutation in a virus, a nick of time, but its future is not restricted start attacking it. new mRNA vaccine can be developed in to vaccines for COVID. Reed and Singh are The development of mRNA has two months. planning to use it for cancer therapy some- far-reaching consequences for All mRNA vaccines provide these ben- time in the future, and their favourite area dealing with future pandemics, efits. The HDT-Gennova vaccine has addi- of infectious diseases. The technology will but there is still a lot that we do tional features that make it even more use- be developed for vaccinating against a not understand. The long-term ful. It is self-amplifying, which means that number of infectious diseases like season- side-effects of mRNA vaccines are it can be given in small doses. For example, al flu, malaria, dengue, West Nile virus, likely to be small, since mRNA while current mRNA vaccines are given at and so on. In fact, scientists at Yale Univer- degrades rapidly, but data need doses between 30 and 100 micrograms, the sity are already working on an mRNA vac- to come from actual patients over Gennova vaccine may be given at less than cine for malaria, also using self-amplifying a number of years. Scientists 5 micrograms. The lower dose has a big im- technology. also would need to see how long pact on manufacturing and price; a reactor Gennova has the capacity to make 100 an immune response will last. that makes self-amplifying RNA can make million doses of the COVID vaccine after For the moment, they are largely 50-100 times more doses with the same re- approval. Singh is planning to ramp up ca- optimistic. 7 actor size. pacity to vaccinate the entire country. 7 29

SHAASTRA 2021 May-Jun 14.indd 29 5/18/21 7:27 PM INNOVATION BORN-AGAIN BUSINESS JAYADEVAN PK When COVID-19 disrupted she approached her mentor and Biocon health tech start-up founder Kiran Ma- Niramai’s revenue model, zumdar-Shaw and asked if she could the company innovated to test the system out secure a lifeline. at Biocon’s office in Bengaluru. Shaw agreed. JAYADEVAN PK FeverTest is now able to pick out EETHA MANJUNATH was happy people with fever that her health tech start-up Ni- from a distance, ramai was finally taking off after so no one needs to four years of hard work. She had come in contact Gleft the corporate world after 25 years, to with a potential start this company in 2016. It was person- COVID-19-positive al: two of her relatives had been diagnosed person. Several with cancer, both at late stages. That’s not buildings in Ben- unusual: one in every 12 women is at the galuru, including risk of developing breast cancer, a leading more than 20 from cause of cancer deaths in the world. In the builder RMZ, most cases, breast cancer is detected in lat- and the offices of er stages, when it’s too late. The problem Morgan Stanley vexed Manjunath, who led the data analyt- and Kotak Mahin- ics lab at Xerox Research Centre India, and Nirmai’s thermal scanner deployed at a tech park in Bengaluru. dra Bank in Mum- she came up with a low-cost solution that bai have deployed could be used to detect cancer in the early the contactless stages. And Niramai was born. similar methods, can people entering a screening solution. The camera can also Starting up was hard. But things picked building be screened for fever, a symptom pick out people from a crowd if they aren’t up as the company hacked away at the of COVID-19? wearing a mask. It can cost up to `6 lakh problem, and Niramai’s artificial intel- “During the lockdown, it became a to deploy a full-feature solution capable ligence-based breast cancer screening guideline that anyone entering an office of detecting fever even if several people solution gained acceptance. The idea was space should be screened for fever. We used are walking by at the same time. A mobile to use an infrared camera to measure thermal cameras for our daily living, and I version of the solution costs up to ₹`1 lakh. temperature variations on the chest and felt we could do something about this,” re- “There are also monthly subscription to identify patterns that can detect abnor- calls Manjunath. Infrared thermometers models, so it can be deployed widely,” said malities as opposed to the traditional way were prone to errors. Sometimes readings Manjunath. The system can detect tem- of using X-ray mammograms or Magnet- differed based on the distance at which the perature with an accuracy of up to 0.5ºCel- ic Resonance Imaging (MRI). Regulatory infrared thermometers were kept. sius and flag someone without a mask 98 approvals were in place, and more than per cent of the time. 30 hospitals had deployed the solution. The start-up had ten US patents to its The same technology NEW REVENUE STREAM name. More than 30,000 women had been used to screen patients “It started as an experiment, but it has be- screened for breast cancer with Niramai’s come a new product and a revenue stream solution. Venture capital firm BEENEXT for cancer is being for us,” said Manjunath. had invested $6 million in the company in In January, this writer walked into one 2019. Now it was time to go big. harnessed in COVID-19 of the many buildings at RMZ Ecoworld, But then in March 2020, the company times to scan crowds for a 77-acre special economic zone in subur- suffered a blow. The COVID-19 pandemic ban Bengaluru. Every day, thousands of raged across the world. In India, the gov- high temperatures. employees stream into technology compa- ernment enforced a rigorous lockdown, nies housed in these buildings. Manually and the healthcare system was put in The Niramai team wrote up a new soft- screening everyone for COVID-19 symp- disarray. “There was a sharp drop in the ware, FeverTest. With this, people entering toms would have been virtually impossi- number of screenings, particularly in hos- a building could be screened from a dis- ble. But there it was, a camera behind the pitals, as people didn’t want to go in for tance. The thermal camera would capture receptionist’s desk, along with safety per- non-critical tests,” recalls Manjunath. temperature data from people and relay it sonnel, effortlessly temperature-scanning to a computer; FeverTest would identify people entering the building. Occasionally, THE SMART PIVOT people with abnormal temperature. But a robovoice called out to a maskless pass- But Manjunath and the team were quick temperature could not be the only marker erby: “Please wear a mask.” FeverTest ap- to connect a new market need with their to screen for COVID-19. So the team also pears to be doing its job. As we enter the expertise. Given a set of images captured analysed breathing patterns and baked post-pandemic world, in which epidemiol- by a thermal camera, Niramai’s system, that into the solution. “All this is done in a ogists predict the occurrence of COVID-19- called Thermalytix, could discern breast seamless fashion, as with a CCTV,” Manju- like diseases, solutions like Niramai’s may cancer. The question now was: by using nath said. With the new solution in hand, yet become a permanent fixture. 7 30

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SHAASTRA 2021 May-Jun 14.indd 31 5/18/21 7:27 PM BIG DATA

WHERE INDIA STANDS ON RESEARCH AND INNOVATION

The break-out in China’s growth was also accompanied by a break-out in its research and innovation. India has made strides in research and innovation, but it continues to be held back by several fundamental factors.

HOWINDIALIVES.COM NNOVATION IN India has a glorious 1 The Ranking civilizational history. The legendary Wootz steel, which traces its origins RANK 2011 62 29 16 47 7 back to parts of southern India, in 80 Ipresent-day Tamil Nadu, in the first mil- 2012 64 34 21 58 10 60 lennium BCE, bears testimony to ancient 2013 66 35 18 64 5 India’s steel-making prowess. The name 40 2014 76 29 16 61 6 Wootz is believed to be the Anglicised 20 derivative of urukku or ukku, the Tamil 2015 81 29 14 70 5 and Kannada words for steel, respective- 2016 66 25 11 70 4 ly. There are countless other such monu- 2017 60 22 11 69 4 ments to Indian ingenuity. But in the more modern era, India’s 2018 57 17 12 64 6 track record of innovation has been char- 2019 52 14 11 66 3 acterised by sobering underperformance. On the metrics scales that grade countries 2020 48 14 11 62 3 on the pillars that support innovation, In- INDIA CHINA S KOREA BRAZIL US dia punches below its weight, particularly Source: Global Innovation Index reports, 2009-2020 when compared to its peer, China. We dis- sect these data sets to understand what it INDIA WAS RANKED 48 in 2020 in the Global Innovation Index, a quantitative and multi-di- might take for India to build an innovative mensional capture of how innovative a country is. But its own path over the past decade society. 7 stands in contrast to China, which has constantly improved its rankings, and South Korea and the US, which have maintained their lead in innovation. India’s journey is more akin to howindialives.com is a database and Brazil, another large country with huge promise. The answer to why India has trodden this search engine for public data path lies in several upstream factors, ranging from universities to government funding of research and development to researchers.

SHAASTRA 2021 May-Jun 14.indd 32 5/18/21 7:27 PM 2 The Base 11 Number of science universities in the top 500

34 128 24 17 2 10

101 91 8 17 16

12 9 35

Engineering & Technology Life Sciences & Medicine Natural Sciences

US CHINA INDIA SOUTH KOREA BRAZIL

Source: QS World University Rankings 2020

A. TOP UNIVERSITIES UNIVERSITIES PLAY AN IMPORTANT ROLE in the innovation ecosystem. The role played by Stanford in the Silicon Valley ecosystem is well-documented. China’s rise as an innovation powerhouse was also accompanied by an improvement in the quality of its universities. India has about half a dozen universities in the top 100 of the QS World University Rankings 2020 in three broad domains of science. What it lacks is depth, as underscored by the yawning gap between its elite universities and an average university.

Doctoral degrees in science and engineering Researchers in R&D (per million population) 7980 39900 34600 34400 31400 5331 26100 4412 3885 3496 13800 13800 2287 7800 1307 6100 5500 888 885 4400 686 2900 539 295 253 156 110

US CHINA INDIA SOUTH KOREA SOUTH KOREA US CHINA BRAZIL INDIA 2000 2010 2015 2000 2010 2018

DOCTORAL DEGREES RESEARCH POOL

Note: Data for Brazil not available Note: Researchers here are professionals who conduct research and improve or develop concepts, theories, models, techniques, instrumentation, software of operational methods. R&D covers basic research, applied research, and experimental development. Source: OECD, Education and Training Indicators, 2019; National Bureau of Statistics (China), China Statistical Yearbook (various years) Source: World Bank (which has, in turn, sourced it from UNESCO Institute for Statistics)

B. DOCTORAL DEGREES C. RESEARCH POOL WHILE THE NUMBER of doctoral students in India has increased in AMONG THE five select countries, India has the lowest number of the last 15 years, two things stand out. One, China has widened its researchers in research and development as a share of population. lead over India significantly. Two, India’s growth has stagnated. Be- This is to be expected in a country where only one in four persons in tween 2010 and 2015, there’s hardly been any growth in the annual the college-going age bracket goes to college. That said, the number number of doctoral students India produces, which is at odds with of researchers per capita is growing, suggesting that India is able to what more innovative countries have done. attract more people into research. 33

SHAASTRA 2021 May-Jun 14.indd 33 5/18/21 7:27 PM D. R&D EXPENDITURE Gross domestic expenditure on R&D ($ billion, adjusted for PPP)

2000 2005 2010 2015 495.1 408.5 407.5 326.2 268.6 213.5 76.9 49.7 86.8 52.2 43.7 30.6 33.1 26.5 18.5 15.7

UNITED STATES CHINA SOUTH KOREA INDIA Note: Data for Brazil not available Source: NCSES, National Patterns of R&D Resources; OECD, Main Science and Technology Indicators 2019/1; UNESCO Institute for Statistics, Research and Experimental Development data set.

3 The Output A. SCIENTIFIC AND TECHNICAL JOURNAL ARTICLES B. SHARE IN TOP 1% CITED ARTICLES BETWEEN 2000 and 2018, India has seen a four-fold growth in HOWEVER, numbers alone don’t suffice. Influence also matters. In the number of journal articles in scientific and engineering areas. terms of its research being cited in the top articles, India was on par During the same period, China saw a near 10-fold growth. with China in 2005. But India has stagnated since, while China has gained significant traction.

No. of articles in scientific Index of highly cited articles & technical journals 528263 1.95 1.91 1.77 1.77 422808 408817 312517 304782 1.05 1.02 0.83 0.82 0.66 0.65 0.63 0.60 0.61 135788 0.50 0.41 0.37 62437 66376 60148 53064 50589 41666 21771 15905 12783

CHINA US INDIA SOUTH BRAZIL US CHINA SOUTH INDIA KOREA KOREA 2000 2010 2018 2000 2005 2010 2015

Note: Citation counts for a year are the number of citations in peer-reviewed literature for articles published in that year. At least 2 years of data after publication are needed for a meaningful measure. This figure depicts the share of publications that are in the top 1% of the world’s citations, Note: Data refers to the number of scientific and engineering articles published in the following relative to all the country’s publications in that period and field, referred to as the “index of highly fields: physics, biology, chemistry, mathematics, clinical medicine, biomedical research, engineering cited articles.” Data for Brazil not available. and technology, and earth and space sciences. Source: NCSES, special tabulations (2019) by SRI International and Science-Metrix of Elsevier’s Source: World Bank Scopus database

C. INTERNATIONAL COLLABORATIONS INTERNATIONAL COLLABORATION is both a lagging indicator of the quality of research and a leading indicator of future research. In 2018, among the top 15 producers of science and engineering articles, India trailed in international collaborations.

215000 UNITED STATES 331000 Number of articles 127000 CHINA 456000 100000 UNITED KINGDOM 61000 82000 GERMANY 72000 61000 FRANCE 43000 51000 CANADA 41000 51000 AUSTRALIA 34000 50000 ITALY 49000 42000 SPAIN 37000 36000 JAPAN 83000 27000 INDIA 123000 25000 BRAZIL 48000 22000 RUSSIA 72000 22000 SOUTH KOREA 56000 13000 IRAN 41000 International collaborations Domestic author(s) only

Source: NCSES, special tabulations (2019) by SRI International and Science-Metrix of Elsevier’s Scopus database Note: An article is considered an international collaboration when there are institutional addresses for authors from at least two different countries. 34

SHAASTRA 2021 May-Jun 14.indd 34 5/18/21 7:27 PM GUEST COLUMN

INNOVATE TO ACHIEVE SCALE How India can make the most of a post-COVID geo-economic landscape and set itself up as an innovation hub. FUNTAP / 123RF

PAWAN GOENKA

EVER WASTE a good crisis. That ‘com- mandment’ acquires compelling sig- Nnificance for India as it comes to term with an evolving geo-economic landscape in the light of the COVID-19 pandemic. The severe disruption in the global manufacturing value chain last year, as a consequence of the gravest public health emergency in a century, has prompted countries around the world to reflect seriously on the need Investments in technology-led about value for money; and China’s is about to diversify their manufacturing base. And innovation and in building capacity scale. The answer to that question will lead although the ill-effect of the pandemic is – ahead of ‘volume visibility’ – are to a realisation about what it will take to still not fully behind us, the prospect of a re- make buyers from large developed econo- alignment of the manufacturing value chain the key if India is to take the lead mies make a beeline for India. around the world holds enormous potential in sunrise sectors of tomorrow. India’s aspiration to become a global hub for India. Indeed, in some ways it is a god- for technology and manufacturing in select sent opportunity for Indian manufacturing lack of global scale, which is perhaps a func- industries can be realised – with greater in- to demonstrate its prowess. tion of the fact that investment decisions vestments in technology and capacity-build- It appears that the Indian government is have in the past been very conservative. In- ing. Currently, India invests barely 1% of sensitive to the fierce urgency of the pres- dia also has cost disadvantages because of GDP in R&D, against South Korea’s 4%. ent moment and is keen to seize this once- the relatively higher costs of power, logistics Furthermore, in Korea, nearly two-thirds of in-a-lifetime opportunity. The campaign for – and funds, and the burden of excessive reg- the R&D investment is made by industry; in atmanirbharta channels that positive sen- ulatory compliances. India, it is only a third. timent and looks to build on India’s manu- The effect of this shows up starkly in In- China’s manufacturing muscle was facturing strengths (where they exist) and to dia’s sub-par performance in high-tech man- shaped by a ‘build it and they will come’ remedy any failings there may be. ufacturing. The country’s share of global mindset. On the other hand, Indian manu- The areas of success – and inadequacies high-tech trade is under 1%; comparative- facturers typically wait for volume visibility – in Indian manufacturing are somewhat ly, China’s is 26%, Germany’s is 8.3%, and before embarking on capacity expansion. self-evident. The automotive industry and South Korea’s is 7.7%. India’s high-tech ex- That gives birth to a chicken-and-egg situ- the pharmaceutical industry represent two ports are about $20 billion, barely a fourth of ation. Many global manufacturers want to of the more striking examples of success. Vietnam’s. And India does not have a strong relocate to India, and are looking for plug- Since the reforms of 1991, the auto industry manufacturing brand, and given that invest- and-play infrastructure, but we don’t have it has grown at a compounded annual growth ment in R&D is inadequate, there are very because we haven’t invested adequately in it. rate of 8.2%, and today accounts for nearly few sectors in which Indian companies own half of manufacturing GDP. And 27% of the cutting-edge IPR. MINDSHIFT NEEDED industry’s output, by value of vehicles and Given these sobering realities, how best The road to atmanirbharta is long and hard. components combined, is exported. The sec- can India grab a fair share of global manu- It is often easier to import than to commit tor has a highly integrated ancillary base, facturing, and enhance its high-tech exports to local value-add. It is also easier to buy or invests substantially in R&D, and generates profile? license technology as opposed to developing employment for an estimated 37 million peo- it ourselves. More generally, it is easier to ple, directly and indirectly. INNOVATION IS THE KEY follow than to lead. To my mind, the key to achieving these is to But that mindset needs to change. India has RECIPE FOR SUCCESS invest in technology-led innovation and in several things going for it – among them a big As Chairman of the Steering Committee capacity. Until now, manufacturing exports domestic market, abundant natural resourc- for Advancing Local Value-Add and Exports from India have centred on cost-competitive- es, a large pool of working-age population, a (SCALE), set up by the government to propel ness. With time, many emerging economies strong private sector, and strategic geo-loca- manufacturing growth in some champion have caught up on manufacturing capabili- tion. With a tweak of the passive mindset, sectors, I have been looking up-close at the ties and now offer equally competitive man- and by firming up our resolve, India can take factors that have contributed to such manu- ufacturing bases. Cost consideration will no the lead in several sunrise sectors. 7 facturing successes in India. doubt continue to be important, but to se- However, for all the inherent strengths of cure a greater global market share, we need Until recently Managing Director of Mahindra Indian industry, I believe that a change of those investments in innovation. & Mahindra, Pawan Goenka is Chair of mindset – away from the incrementalism of The question for Indian manufacturers the Government’s Steering Committee for the past – is imperative if we are to achieve to ask themselves is: what is our narrative Advancing Local Value-Add and Exports the goals we have set for ourselves. Specifi- for exports? Germany’s is about technology; (SCALE), and Chairman of the Board of cally, Indian manufacturing suffers from a Japan’s is about quality; South Korea’s is Governors of IIT Madras and IIT Bombay. 35

SHAASTRA 2021 May-Jun 14.indd 35 5/18/21 7:27 PM LAB JOURNAL Smothering the flames of instability Scientists at IIT Madras channel an intuitive understanding of complex system dynamics to solve the problem of ‘combustion instability’.

KANNAN KRISHNAMURTY ADITI JAIN

NE NIGHT in August 2013, R.I. Sujith, a professor of aerospace engineering at IIT Madras, uncharacteristically awoke just before 3 a.m. in a state of Ointense excitement. He had just had an epiphany of sorts – although the scientist in him would probably say he experienced a ‘Eureka!’ moment. The ‘revelation’ he had related to one of the most vexing problems in his field of study: how to stop small fluctuations in flames from becoming large and destroy- ing gas turbines and rocket engines. A month earlier, Sujith, who researches combustion instability, especially in turbines and rocket engines, had attended a conference in Hyderabad. The conference was on non-linear dynamics, an area of research for mathematicians and theoretical physicists. One dealt with hardcore engineering, the other with abstract mathematics. In that sense, it was an unusual conference for an engineer to attend, but Sujith had sensed a connection between these two fields and wanted to learn non-linear dynamics and complex networks. The ‘combustion instability’ problem that Sujith had been pondering was as old as the subject itself. Engineers who designed the rockets for the Apollo Mis- sion had got around it by conducting 3,200 full-scale tests that taught them how to Combustion instability Prof R.I. Sujith at work in his laboratory design engines where flames were not at IIT Madras. self-destructive. But they had merely side- affects gas turbines and stepped the problem: they did not under- jet and rocket engines, complex networks, was a long-haul proj- stand the mechanism of flame instabili- ect. “Knowing is not understanding, being ties. Five decades after the Apollo Mission, and Sujith’s team’s work able to calculate everything,” he says. “I engineers were still trying to understand am still at it.” how flames become unstable in turbines used a complex network In 2014, Sujith began to use the math- and rocket engines. approach to address it. ematics of complex networks in his re- That August morning in 2013, the pos- search. His paper, published in 2015 in the sible reasons for combustion instabilities Journal of Fluid Mechanics, was the first came to Sujith in a flash. “It stayed for a take a long time to work out. Specifically, paper in thermoacoustics or combustion few minutes… the feeling that I knew ev- he understood that complex networks – for that used complex networks.. The field is erything,” recalls Sujith. He immediately instance, airline routes, the World Wide now growing very fast, with scientists and wrote down what he could remember. Web, the food chain – share features with engineers using complex systems mathe- flames. However, he had to translate his matics to understand combustion dynam- FROM INTUITION TO EQUATION intuitive sense into a set of equations that ics. In the past five years, Sujith’s group Sujith had intuitively felt the connection could be solved. Developing these equa- has produced several insights that could between complex networks and instabili- tions, which would describe the behaviour help turbines and jet engines improve ties in combustion, but the details would of combustion using the mathematics of their performance. 36

SHAASTRA 2021 May-Jun 14.indd 36 5/18/21 7:27 PM RANGGA173/123RF.COM Combustion instability can af- Now, with the complex network fect turbines and jet and rocket principles, Sujith found an inter- engines – with disastrous conse- mediate stage before the full insta- quences. Jet engines avoid the bility happened. problem by severely restricting Sujith’s team found that upcom- the conditions of flight. In other ing instability in the combustion realms, combustion instability system can be predicted by the na- can cause turbines to be shut ture of oscillations. When the sys- down, entailing revenue loss for tem is stable, the oscillations are utility companies. small in amplitude and aperiodic; In other words, this was an im- then, in the intermittent stage, portant problem to solve. People’s there are bursts of large-ampli- lives depended on it, and so did tude oscillations; and finally, in business fortunes. the unstable stage, the oscillations are periodic but with large THE BIG PICTURE amplitude. This movement from Sujith’s special research interest small-amplitude to large-ampli- was thermoacoustic instability, tude periodic oscillation is actual- a phenomenon where the sound ly the movement of a system from produced by the engines effec- a complex network to a regular tively enhances the flames de- network: a network where every structively. While this problem node has a similar number of has been around for a while, engi- connections and hence the system neers largely took a reductionist has no large hubs which can influ- approach to get rid of the noise. ence the whole network. Sujith’s team, however, decided to look at the issue holistically using PUTTING OUT THE FIRE a complex network approach. “I Sujith’s team was therefore able decided that this part-by-part ap- to successfully predict the upcom- proach cannot be applied to solving disaster; its next aim was to ing the thermoacoustic problem get rid of this instability. They de- as the oscillations generated in cided to again apply the complex the system form a complex net- network approach to mitigate the work and influence each other,” upcoming instability. says Sujith. “In Kalari martial arts, if specif- A complex network has a large ic pressure points of an opponent’s number of closely interacting body are poked, the rival is unable parts that produce effects not easi- In complex networks, individual to move any body part. This is be- ly predictable by studying its com- nodes are connected to each other cause the particular body part that ponents. In fact, a complex system has been poked is like a hub and follows the metaphysical dictum in such a way that the whole is more has connections with various other that the whole is more than the than the sum of its parts. vital body parts or function. We de- sum of its parts. Complex net- cided to find such a point or hub in works are all around us: the neu- the system which if perturbed can rons in our brain connected by synapses, that a few web pages have a large number restore back the system,” explains Sujith. billions of computers and mobiles con- of connections. Sujith’s first paper using Sujith’s team found a way to identify nected through the World Wide Web, and complex networks found that combustion regions that were critical to controlling living organisms at various levels linked noise was scale-free. instability. Microjects injected in those through the food webs. Individual ele- In simple terms, this meant that the regions can reduce the amplitude of the ments (or nodes) in the networks are con- vortices that form while burning have no oscillations at the intermediate stage to a nected to each other. Just over two decades preference for any size. Sujith and his stu- level that is comparable to what is observed ago, scientists made an interesting discov- dents converted the data that they got from during the state of stable operation. This ery about these networks: some nodes have combustion into complex networks by us- injection in the critical region can stop the only a few connections while others have a ing specific algorithms, and showed that it turbine’s path from stability to instability large number of connections. exhibits scale-free characteristics. It also and prevent blasts and other disasters. This fact seemed counter-intuitive in gave Sujith a method to predict when it is In parallel, Sujith also found another the beginning. Why should some nodes in about to lose its scale-free nature. It often feature of complex systems during his com- a network have more connections than the means trouble for the engine or turbine. bustion: chaos or lack of order. Although others? It turned out that any network that During experiments in combustion, counter-intuitive, nature is chaotic and yet keeps growing can exhibit such a feature Sujith had noticed that the faces of his stable. Lack of chaos often means trouble. when there is a preferential attachment students became tense before the onset A healthy heart is chaotic, and loss of this to one node. A preferential attachment of thermoacoustic instability, when the feature is a sign of impending problems. A means that some web pages generate more sound produced while burning interacts well-burning flame is also chaotic, and loss interest than others, or some companies with the flame to produce vibrations and of this feature is also a sign of trouble, just are able to produce more partnerships, and noise. Such vibrations can produce cracks like loss of scale-free behaviour. so on. Such networks are called scale-free in the wall of the engines or cause un- Chaos and scale-free behaviour are now networks, in contrast to a random network steady burning in the engines. The stu- established as important features of flames where no node dominates. The World Wide dents, who perform a large number of ex- that are stable. But scientists are yet to re- Web was supposed to be a random network periments in the lab, could somehow sense late them to each other. That is where Sujith – until experiments showed otherwise, the onset of instability before it happened. wants to take his research in the future. 7 37

SHAASTRA 2021 May-Jun 14.indd 37 5/18/21 7:27 PM SPECIAL FEATURE THE BOLD NEW BIOTECHPRENEURS A handful of Indian start-ups is venturing into the high-risk, high-attrition pursuit of new drugs, enabled by an emerging ecosystem.

GAURI KAMATH If this sounds familiar, well, it is. antibiotics into human trials, to combat Through the 1990s and the early 2000s, the dual global threats of drug-resistant HILE pursuing her doc- publicly listed Indian off-patent or generic infection and bioterrorism. torate in skin biology at drug companies embarked on this journey. Also in Bengaluru, Zumutor Biologics is the National Institute of With hoary multinational drug companies lining up a pipeline of novel monoclonal Immunology, in New Del- such as Merck and Pfizer as their model, antibodies (mAbs) against cancer, with a hi, Parul Ganju’s research they built lavish laboratories, paid top dol- potential first-in-class mAb for prostate Wled her to people living with vitiligo. This lar for talent and seemed set for the long cancer inching close to human trials. is a disease that causes visibly discoloured haul. After all, it takes an average 10 years And in Chennai, Sekkei Bio is design- patches on the skin and hair resulting for a drug to go from lab to market. ing novel insulin, which can withstand from the loss of melanocytes, the skin’s But the stock market ran out of patience. the harsh environment of the gut, for oral pigment cells. It has no known cure. As she Eventually, barring some exceptions, they delivery, and dual agonist peptides. Sekkei heard their stories of social stigma, Gan- scaled back or shuttered their discovery combined forces with another start-up, ju’s academic interest turned into a deeper operations to focus on the core business of Quest Compbio, which had computational need to make a positive impact. “The effect generics. biology expertise and an interest in neuro- of this disease was humongous, and they pathic pain relief. were waiting for something to work.” “Small companies are definitely pushing Ganju could have gone on to build a ca- The new players on the hard,” says T.S. Balganesh, a veteran sci- reer in academia; after her PhD, she won entist who has led innovative R&D efforts a prestigious government scholarship drug discovery landscape in both government and industry. “There meant to encourage young scientists in have interests that span are credible people behind them who are basic research. Yet, she was convinced driven by passion and science.” that for research to turn into solutions, a a range of therapy areas. In their stories lie clues to India’s evolv- corporate structure was needed. In 2016, ing drug discovery landscape. therefore, Ganju partnered with Krish- But their goal is similar: “It is ideas – and not concrete, iron and namurthy Natarajan, collaborator on her to discover a new drug steel – that should make us,” says Anand PhD project and a professor in the School Khedkar, co-founder, Sekkei Bio. Khedkar of Life Sciences at Jawaharlal Nehru Uni- and take it to the global spent two decades leading an ambitious versity, to start Pune-based Ahammune market. project to develop insulin tregopil for oral Biosciences to discover dermatological administration in the well-equipped – and drugs. well-funded – R&D lab of Bengaluru-based In August 2020, Ahammune applied to Drug discovery is an expensive, high- Biocon before he quit to start Sekkei with the Indian drugs regulator for approval risk pursuit. According to a 2020 study co-founder Monalisa Chatterji, also a for- to start first-in-human clinical trials on published in the Journal of the American mer senior scientist at Biocon. At Sekkei, a topical drug for early stages of vitiligo. Medical Association (JAMA) Network, of they run a lean ship, with a team of less In pre-clinical tests, the drug was shown 63 new drugs approved in the US between than 10, and hire consultants and vendors to arrest disease spread by targeting the 2009 and 2018, the median capitalised cost for a range of R&D services. starting point of a cascade of immune of R&D was $985 million per drug. This ac- events that kills off melanocytes. It was counts for failures as well. A 2019 analysis FRUGAL INNOVATION like “cutting fuel to the fire,” says Ganju. in Nature Reviews Drug Discovery found Companies such as Sekkei differ in im- that the chance of success for a compound portant ways from the pioneers. Their THE NEW ADVENTURERS entering Phase 1 trials has remained founders have wagered a considerable bit Ahammune is the latest green shoot in the slightly under 10 per cent over the past two of their savings, sold off ancestral proper- new drug discovery landscape of India. decades. ty and knocked on many doors for funding. There are a clutch of others. Some began Yet, this relatively new breed of drug Ergo, upfront capital and human resource earlier, others are nascent. Their interests companies is inspiring hope, combining investment have to be kept to a minimum: span a range of therapy areas: drug-resis- an appetite for risk with quality science. no lavishly built labs or large teams here. tant infection, cancer, rare disease, and Take Noida-based Curadev. It has won This is actually feasible for two reasons. metabolic disorders such as diabetes. The early validation for its efforts in immu- Firstly, over the past decade, government people behind them could be freshly mint- no-oncology out-licensing its molecules labs and educational institutions such as ed post-docs or seasoned drug industry to Bayer, Takeda and Roche. Or consider the Indian Institutes of Technology (IITs) professionals. Yet, their goal is the same: Bengaluru-based Bugworks Research, have set up innovation incubators. Incu- to discover a new drug and take it to the which is on the cusp of putting the first of batees can rent access to well-maintained, global market. a completely new class of broad-spectrum even cutting-edge, lab equipment costing 38

SHAASTRA 2021 May-Jun 14.indd 38 5/18/21 7:27 PM JIGNESH MISTRY

Dr Parul Ganju, Co-founder & Executive Director of Ahammune Biosciences, at her If drug discovery has to to the largest early-stage biotech funding lab at the NCL Innovation Park in Pune. programme in India in the form of the thrive in India, it needs Biotech Ignition Grant (BIG). BIG awards upto `50 lakh to projects with commercial- crores of rupees. Additionally, they are more local avenues of isation potential to reach proof-of-concept assisted to meet various business-related financing. And generics in 18 months. Nearly every start-up inter- compliances. “We want to dedicate all our viewed for this piece is a BIG grantee. energies and resources to the science,” companies must take a Put all this together, and you see the says Ganju, whose company is based at makings of an ecosystem that was large- the National Chemical Laboratory’s Ven- more active interest in ly absent when Indian pharma companies ture Center. “Being in the incubator has Indian R&D. first made efforts to discover new drugs. allowed us to do that.” “In the last few years, the ecosystem has In Bengaluru, the Centre for Cellular definitely catapulted to where it is now,” and Molecular Platforms (C-CAMP), a have now become an important piece of says Kavitha Iyer Rodrigues, founder and science-based innovation hub, located in the Indian discovery ecosystem. CEO, Zumutor, who counts Biocon and India’s biggest bio campus, uses rigorous The CRO industry is one reason why Millipore among her former employers. selection filters for incubation and fund- companies such as Curadev can hit the This is giving smaller companies a fight- ing. This helps “start-ups make their sto- ground running, says Arjun Surya, ing chance. Yet, considerable challenges ry stronger,” says Taslimarif Saiyed, CEO co-founder. “When you find a promising remain. and Director. “We also constantly ask in- molecule, you have to put everything be- novators to show us how they are building hind it,” he says. “This may include ex- THE DOWNSIDE RISKS global innovation.” pertise you don’t have.” Before Curadev, The virtual model, as we have seen, has When co-located with other scientific in- Surya set up and helmed the biology unit many benefits, but it is not always effi- stitutes of excellence, incubators facilitate at TCG Lifesciences, a CRO. At Curadev, cient. Firstly, expertise, for the most part, a free flow of ideas within the community he used his former employer’s chemistry is scattered across CROs. and are avenues of learning and collabo- services, among other things. A CRO that is good at active pharma- ration. This makes it possible to have a ‘virtu- ceutical ingredient (API) synthesis may be al’ model that prioritises owning the tech- new to analytical method validation or for- AN ENABLING ECOSYSTEM nology and the intellectual property while mulation development and animal work. Secondly, almost in parallel, a robust con- outsourcing much else, says Chaitanya Each step calls for transfer of knowledge. tract research industry, delivering drug Saxena, CEO, Shantani Proteome Analyt- “Information gets lost in translation,” says discovery and development-related ser- ics, an early Venture Center incubatee. Ahammune’s Ganju. vices to pharma and biotech companies, This model also has its downside, but For some services, companies have to look has emerged in the private sector. From more on that later. outside India. Shantani’s Saxena did this to animal testing to chemical synthesis and Funding is another critical component, screen diabetes compounds on pancreatic formulation development, the Indian con- and the Indian government, too, does its islet cells isolated from cadavers. Sekkei’s tract research organisation (CRO) indus- bit. Through the Biotechnology Industry Anirudh Ranganathan, who founded Quest try offers a suite of services for a fee. Set Research Assistance Council (BIRAC), an Compbio, relied on academic contacts in up primarily to do business with Western initiative of the Department of Biotech- Austria and Canada for in vitro assays for companies that offshore to save costs, they nology (DBT), it has committed `250 crore its neuropeptides programme. 39

SHAASTRA 2021 May-Jun 14.indd 39 5/18/21 7:27 PM SPECIAL FEATURE

rus Lifesciences chose to assign IP around coordinate clinical development. “Drug STRADDLING a promising portfolio of molecules with discovery has to be front-ended in the US/ potential in a rare disease to its US spin- Europe as they are the best for biotech-re- CONTINENTS off Oraxion Therapeutics. In 2018, Oraxion lated work and raising capital,” says entered into a $125-million option-to-li- co-founder Swaroop Vakkalanka. This was START-UPS are increasingly moving to cence agreement with a US biopharma for made easier as Rhizen’s co-owner, drug a hybrid model, which involves a limited these assets. Since then, Aten has also company Alembic, already had a holding presence in some form in Western coun- spun-off Avammune Therapeutics in the firm in Switzerland. For all these firms, the tries known for a mature and well-devel- US for its oncology research. The US spin- R&D still happens here. For instance, Zu- oped drug discovery ecosystem. Zumutor offs give investors a therapy focus and mutor has 36 scientists occupying 16,000 Biologics, which is researching novel the prospect of a smooth exit, says Aten square feet of lab space in Bengaluru and antibodies for cancer, was incorporated co-founder Aditya Kulkarni, admitting a small co-working space in Boston where in Bengaluru in 2013, but two years on that this was not the initial plan. “The it has hired a few consultants. Rhizen’s was ‘flipped’ into becoming a US holding model evolved with time based on where Hyderabad affiliate Incozen Therapeutics company. “We wanted to protect our IP the opportunity lies and the best way to is where a team of roughly 45 is engaged and raise venture funding from investors capitalise.” in pre-clinical R&D and chemistry pharma- who understand the ‘novels’ play,” says The early mover was Rhizen Pharma, cology, while in the US, Rhizen is focussed Kavitha Iyer Rodrigues, founder and CEO. which was incorporated in Switzerland on clinical studies, corporate development Five years ago, Bengaluru-based Aten Po- in 2009, and later opened a US arm to and partnering activity. 7

And for some services, such as Chemis- to plough a good chunk of the payout back drug discovery or are equipped to perform try, Manufacturing, and Controls (CMC) into R&D, says Surya. “We are a boot- due diligence on such start-ups, says At- or scale-up, start-ups have to be cautious strapped company,” he points out. “The en’s Papaiah. “They want a lead investor about revealing business-critical know- government is well-meaning, but the cash with healthcare experience, but there may how, says Khedkar. “There is a concern is just not enough.” His point: innovation be just one or two such investors in the en- that someone else might understand your needs other sources of support. tire country.” idea and move much faster than you.” Sec- Private investment that understands ondly, Indian CRO services are fee-based, THE NEED TO DIVERSIFY the risk and timelines of drug discovery with no option of risk-sharing. Ganju In the meantime, back-up molecules need is available – but in the US and Europe, found that the rates were fixed keeping to be readied, which too needs funds. where funds worth several million dollars Western clients in mind. Shantani learnt this the hard way: it put are raised specifically for early-stage dis- The more dire worry, however, is the ev- everything behind its one asset, a diabetes covery ventures. Can they tap into that? er-present spectre of eventually running molecule. When it could not get licensed, out of funds. Beyond BIRAC, there are the company nearly went belly-up. It had BIG BUCKS BEYOND BORDERS “gaps in the funding ecosystem in India,” to pivot to becoming a discovery services “Without the support of global investors observes Premnath Venugopalan, director, company to earn. “For start-ups that rely and government grant agencies, we would Venture Center. Discovery companies any- on a single asset, if it doesn’t work out, have closed shop,” says Anand Anandku- where in the world look to take the mole- you’re out,” says Saxena. mar, CEO and co-founder, Bugworks Re- cule up to a point where it can be licensed True, costs may be relatively lower to search, a company with promising mole- for upfront and milestone payments to a start with. As Sekkei’s Anirudh observes, cules for anti-microbial resistance (AMR) large pharma company with the experi- the initial cash burn for the oral insulin and biothreats and a case study in suc- ence and big bucks to take it from clinical programme was 20-30 per cent of what it cessful global networking for science and development through to approval. might have been say, in Sweden, where he finance. In addition to seed funding from The further the asset is in the R&D completed his PhD. But when it gets clos- BIRAC/DBT and Indian angel funding, chain, the higher its chances of snagging er to IND filing, costs begin to get stan- Bugworks has also got substantial grants a valuable licensing deal. The ideal point dardised, he says. from international agencies such as the to court licensing would be Phase 2B or “Private investors need to step in,” says Wellcome Trust and CARB-X, and invest- proof-of-concept (PoC) in humans, where Balganesh. But there is little interest – ments from India’s 3one4 Capital, Baxter the value is several-fold higher than when or risk appetite – coming from venture Ventures, USA, Japan’s UTEC and Global it completes pre-clinical studies showing capitalists, private equity firms and even Brain, and South Africa’s Acquipharma in vitro and in vivo PoC. But rustling up high-networth family offices in India. “Pri- Holdings. “We have connected brick by resources even to file an Investigational vate investment in India prefers informa- brick into a vast global ecosystem in the New Drug (IND) application, that is, seek tion technology, where returns are faster,” AMR research space, allowing us to use regulatory approval for Phase 1 or first-in- says Sriram Shrinivasan, Partner and this network to accelerate our assets.” human trials, is an uphill task. Health Sciences Leader, EY India. “Discov- Zumutor has been flipped into a US com- Larger government schemes such as ery offers higher returns, but the wait is pany and Aten has US spinouts for funding the Biotechnology Industry Partnership longer and there is more uncertainty.” and licensing (see box: ‘Straddling conti- Programme (BIPP), which can fund these, Even within healthcare innovation, nents’). Sekkei has recently raised equity require the company to match the contri- funding flows towards start-ups at the funding from Indian investors, but sees it- bution, notes Arun Papaiah, co-founder interface of information technology and self looking abroad in a few years. Aten Porus Lifesciences, which is pursu- healthcare such as online pharmacies, But everyone agrees that if drug discov- ing research in immuno-oncology. “It be- says Premnath. C-CAMP’s Saiyed adds ery has to thrive in India, it needs more comes extremely challenging to make up that “significant” Series-A funding ca- local avenues of financing. Interestingly, this gap.” pacity needs to be created for “non-tech” most of the suggestions offered require ge- It doesn’t take long to run through a BIG health solutions just to allow companies to nerics companies to take more interest in grant in drug discovery, say companies. get to IND-enabling studies and/or Phase Indian R&D. Balganesh says that generics Curadev has had to licence out molecules 1 for their asset. For the most part, very companies could partner with start-ups to earlier than it would have liked in order few VCs in India have the risk appetite for take a promising molecule to PoC stage in 40

SHAASTRA 2021 May-Jun 14.indd 40 5/18/21 7:27 PM KANNAN KRISHNAMURTY The emergence of innovation incubators in government-funded labs and educational institutions has catalysed this trend: incubatees can rent access to cutting- edge lab equipment, and get assistance to meet business-related compliances.

in 2009, between Alembic Pharmaceuticals and Swaroop Vakkalanka, a senior scientist and former R&D Head of Glenmark Pharmaceuticals. Rhizen struck some early licensing deals, and its first cancer drug, umbralisib, out-licensed to US-based TG Therapeutics, received accelerated marketing approval in the US on February 5, reportedly the first drug discovered by In- dian scientists to do so. More recently, the founders of Aten, too, have attracted investments from a few small-to-mid-sized pharma companies in the oncology programme. However, Papa- iah sees these as exceptions. Iyer Rodrigues of Zumutor says generics companies would like to see “clear risk mitigation” at Phase 1 before they can consider investing. If that hurdle were cleared, she says, then so would global biopharma companies. “It is the early-stage funding that’s missing.”

THE MISSING LINKS The inadequate financing, at least partly, could be the result of not having a critical mass of ideas for investors – Indian or global – to choose from. Most of the academia, with some exceptions, has yet to see the potential of marrying science with commerce in India. Academia is a major source of innovation and start-up activity globally, but not in India. “You need the triumvirate of venture capital, academia and start-ups to not just At the Bioincubator Lab at IIT Madras, Anand Khedkar (right) and Anirudh Ranganathan be in close proximity but feed off each oth- of Sekkei Bio, which is designing novel insulin for oral delivery and dual agonist peptides. er,” says EY’s Shrinivasan. Innovation incubators give start-ups relatively low-cost access to cutting-edge lab equipment. There is much, therefore, that still needs to fall into place. Saiyed of C-CAMP be- humans before licensing it out to Big Phar- pools” using the public-private partner- lieves that “the success of one or two will ma. He observes that many of the leading ship model with contributions from top create an inflection point where riskier ones already have offices in innovation Indian pharma companies and Indian bil- projects will start being supported.” Papa- hotspots such as Boston, scouting for R&D lionaires. These companies would have the iah points out that with Curadev’s licens- assets there. “You need them to do that in right to participate in auctions of the best ing deals and Zumutor’s and Bugworks’ the Indian scenario.” assets created. “We need to shake it up,” he molecules closer to Phase 1, the path is EY’s Shrinivasan suggests the creation says. “DBT seed funding and incubation being paved. of venture funds by generics companies, was version 1.0, but in version 2.0 we need In spite of the pitfalls, the journey is ex- much like Big Pharma has done. “They deeper pockets.” citing, the learning curve steep, the mood have the capability to evaluate the research There is an instance of a generic compa- upbeat. Taking its first drug to IND was a and promoters with a strong feel for num- ny partnering scientists to float a discov- “huge learning experience” for the team, bers.” Anandkumar says that the Indian ery company. Switzerland-based Rhizen says Ahammune’s Ganju. “The next mole- government could create “deep-funding Pharmaceuticals is a partnership, forged cule may take less time.” 7 41

SHAASTRA 2021 May-Jun 14.indd 41 5/18/21 7:27 PM MICROSCOPE

BY SPECIAL ARRANGEMENT

Arun K. Shukla with fellow-researchers at the Biological Sciences and Bioengineering lab at IIT Kanpur. A PRESCRIPTION FOR SAFER DRUGS A path-breaking study, led by scientists at IIT Kanpur, uncovers a critical protein mechanism that holds promise for regulating drug effects.

ADITA JOSHI way, called beta-arrestin 2, which is often functions are. They regulate everything linked to adverse effects associated with from our sensory perceptions – the whiff eveloping drugs that don’t have medication. For instance, with traditional of perfume, the unique taste of umami – to adverse side effects is every opioid drugs, from which the Trevena drug our heartbeats, the working of our brain, chemist’s dream. In August 2020, Oliceridine is derived, these adverse events our ability to fight infections, and even the a small beginning was made to- are related to respiratory and gastrointes- cheeriness of our spirit. wards this lofty goal when the tinal complications. Much of the pioneering research work in DUS Food and Drugs Administration ap- The development of the Trevena drug the study of GPCRs had been carried out proved an opioid painkiller that belonged owes much to Arun K. Shukla, a structural by biochemist Robert J. Lefkowitz and his to a new class of drugs that can selectively biologist at the Indian Institute of Tech- collaborator Brian Kobilka, both of whom activate only one subset of receptors called nology (IIT) Kanpur, even though he did received the Chemistry Nobel in 2012. G protein-coupled Receptors (GPCRs). This not play a direct role in it. That’s because Shukla’s interest in this area had drawn drug, Oliceridine, developed by US-based Shukla has been among the few scientists him, as a post-doctoral researcher in 2006, biopharma firm Trevena, evidently works who contributed immensely to the funda- to Lefkowitz’s lab at Duke University, and by preferentially stimulating signalling mental understanding of how GPCR and to collaborate with Kobilka’s laboratory pathways responsible for therapeutic ef- beta-arrestin 2 pathways work in tandem at Stanford University. Currently an Asso- fect, while reducing – if not cutting off when a drug molecule is presented to a cell ciate Professor and Joy Gill Chair at IIT – the activation of those associated with surface. His subsequent work has been in- Kanpur, Shukla has built on the illustrious adverse effects. strumental in unravelling how the beta-ar- legacy of his exceptional mentors, and his Nearly half the drugs that are in use to- restin triggers unwanted side effects. lab at the Department of Biological Scienc- day work through GPCRs. But there is a Present on the surface of each cell in the es and Bioengineering (BSBE) has contrib- problem. These drugs activate not only GP- human body, GPCRs act as “guardians of uted to research work of enormous signifi- CRs, but also an associated signalling path- the senses”. GPCRs are as diverse as their cance in this area.

SHAASTRA 2021 May-Jun 14.indd 42 5/18/21 7:27 PM OLEKSANDRA NAUMENKO Given the centrality of GPCRs to virtual- in India. Shukla then put together a team ly every aspect of human physiology, they and mentored it for functional character- have become pivotal to the pharmaceu- isation of phosphorylated amino acids in tical industry. And it is this area that the the C-terminal of GPCRs. How does one most recent research work from Shukla’s work out the role for a single phosphoryla- lab, the findings of which were published tion site or a group of amino acids? in Science Advances journal in September The best way is to change the amino 2020, addresses. acid(s) in GPCRs and see what happens The study uncovers structural footprints to βaar activation. This could distinguish in GPCRs that may be utilised to design the sites that may lead to G-protein-based safe drugs. It describes special sites (amino signal from the sites that allow an indepen- acids) in the human vasopressin receptor, a dent signalling via βaar. Researchers Hem- kind of GPCR, which are critical to modu- lata D. Agnihotri and Madhu Chaturvedi lating a mechanism that is central to regu- led the task of bombarding the C-terminal lating GPCRs-mediated drug effects. to create mutations. Shubhi Pandey, a Ph.D. student, recalls: “We mutated many phos- COMPLEX BIOCHEMISTRY phorylation sites in the GPCR C-terminal.” The underlying science of this is a little Baidya adds: “We first mutated a cluster complex. GPCRs are activated after bind- of amino acids TSS (Thr369-Ser370-Ser371), but ing to ligands or agonists (molecules that did not notice any effect on βaar activation bind to other proteins) to send signals in- and binding. However, when we touched side a cell. GPCR signalling occurs through another cluster SSS (Ser362-Ser363-Ser364), we the agency of two main actors: G-proteins, saw a totally disrupted βaar activation. It which bind activated GPCRs to initiate pro- was akin to carpet bombing.” cesses such as action of drugs; and beta-ar- Given the centrality of restin (βaar), which acts as a terminator of GPCRs to every aspect of THE IMPLICATIONS GPCR signalling and returns the receptor This study has established a paradigm on to its original deactivated state after its job human physiology, they the unique role of phosphorylation sites in is done. G protein-coupled receptor kinas- have become pivotal to the GPCR-induced βaar activation at the reso- es (GRKs) act as supporting actors to add pharma industry. lution and specificity of a single site. phosphate molecules to GPCRs (by way Anurag Agrawal, asthma researcher of a process called phosphorylation). βaar and Director, CSIR-Institute of Genomics binds to the phosphorylated GPCR and THE PROTEIN STRUCTURE and Integrative Biology, says: “Their work stops the signalling. To understand the binding process, it helps helps us better understand the framework Curiously, βaar can take one of two to know the structure of the protein. Ev- of GPCR-βaar interaction and biased sig- routes after binding to GPCRs. It can either ery protein is made up of chains of ami- nalling and opens up the path towards stop the GPCR activity, or initiate a sepa- no acids, with C-terminal and N-terminal more effective therapeutics.” Shukla and rate signal to yield a different biological ends, and a core domain. The layers, sheets his team have mapped the vasopressin re- outcome. To put this in the context of drug and folds of amino acids give the protein ceptor as a prototype. The same concept action, it bears considering that there are its unique structure and function. Under- can be applied to any GPCR. about 1,000 GPCRs, many agonists and mul- standing the active structure allows one A group of researchers at Stanford tiple drugs. GPCR activation upon binding to selectively locate which amino acids or University has published similar results a drug may kick in signalling through both parts of the protein interact or bind with (Cell, December 2020) using simulation the G-protein arm and an independent other proteins, and which changes in struc- approaches to demonstrate how phosphor- βaar arm. This may result in biological re- ture facilitate the binding or dissociation ylation sites in GPCRs may affect βaar ac- sponses that may yield beneficial effects or of a protein to/from another one. tivation, binding and signalling. Baidya side-effects, which adds to the element of A few amino acids, named Serine (Ser) says with justifiable pride: “Our wet lab complexity. and Threonine (Thr), are altered through results align with the dry lab simulation The smart workaround would be to alter a process of phosphorylation. This mod- approaches.” the receptor or drug selectively such that ification may govern how GPCR activates The ultimate goal of such research is to only the beneficial arm is activated. This is G-proteins and βaars by forming stable develop drugs. “We need to know how the the concept of ‘biased signalling’, wherein complexes. βaars bind to different phos- receptor looks and how it works and then a synthetic drug is created. These under- phorylated amino acids in GPCRs to design the drug to test in animals,” says standings of GPCR-βaar interactions made achieve multiple conformations, which Sai Prasad Pydi, Assistant Professor at Shukla and his fellow researchers conjec- may lead to varied functional outcomes. If the Department of BSBE at IIT Kanpur. ture that cracking the arrestin code would one can map out these sites, the function of “Starting from the bench to bed, we need be the key. βaars may be modulated to the advantage this whole spectrum of work. (Shukla’s) To do that, the goal is to visualise the of biasing the GPCR signalling. research takes care of the first part,” he GPCR-βaar complex at atomic resolution. Since 2013, when Shukla joined IIT Kan- adds. With the US drug regulator approv- Shukla explains: “Using cryo-electron pur as a research group leader, his team has ing the first biased ligand-μ-opioid agonist microscopy, you will be able to see which carried out several research studies in this oliceridine for pain management in adults, parts of the receptor bind βaar. One starts space. In the first of them, researchers Pu- GPCR ligand biasing could definitely shape with purifying the receptor and βaar, al- nita Kumari and others demonstrated that the future. lows the two to form a stable complex in binding of the N-terminal region of βaar to At IIT Kanpur, Shukla will soon have a a test tube and image the structure using the C-terminal region of GPCR is enough Cryo EM facility funded by the Science and cryo EM.” Mithu Baidya, a post-doctoral to form a stable βaar-GPCR complex to Engineering Research Board. He plans to fellow at Shukla’s lab, who was part of the carry out βaar-mediated downstream func- study multiple drug-GPCR-arrestin com- latest study, says: “This is seminal work; tions (Nature Communications, 2016). plexes and unravel new structural mas- the study describes the structural basis of That study broke new ground for mem- terpieces to realise his long-term vision of GPCR-induced βaar activation.” brane proteins structural biology research designing better drugs. 7 43

SHAASTRA 2021 May-Jun 14.indd 43 5/18/21 7:27 PM INTERVIEW ‘Set ambitious project goals’ Tech investor and BENEDIKT VON LOEBEL/WEF for many of these disorders. These are disorders philanthropist Kris for which we don’t have Gopalakrishnan on the a cure. It will be a large problem in India because wisdom of thinking big on we have a large popula- research and programmes. tion. If we can help solve this problem by adding to the global research, it KRIS GOPALAKRISHNAN retired from will be a contribution to Infosys in 2011 after three decades in the the entire world. IT industry. Since then, he has been work- There will be other ing as an investor and philanthropist, benefits as we do these and especially funding scientific research things. If we set ambi- in high-risk areas. He spoke to Hari tious goals, there will be Pulakkat about what he learned about smaller goals in between. research and entrepreneurship since And I felt that we will be then. Excerpts: able to show results over the years. Some interest- What attracted you to funding science? ing results are coming I wanted to make myself busy. I didn’t and papers are being want to compete with Infosys, and so I published. I am satisfied wanted to reinvent myself. My experi- with the area being cho- ence with the IT industry showed that an sen and the results. emerging technology has a significant impact on the economy and provides huge Many people are fund- opportunities for entrepreneurship if we ing brain research. get in at the right time. I chose the brain. How do you choose I decided to support research, innovation what to fund? and entrepreneurship in emerging areas. I have taken two Over time, I expanded my focus to include approaches. One is healthcare as well. top-down, which is the Centre for Brain Re- What attracted you to biology? search. We have set it up I had to take an area that is going to as an open platform. The change dramatically with the introduc- second approach is the tion of technology; is very broad; will “If we can provide affordable and area of brain sciences have significant societal impact; and will quality healthcare to India, we can where I have set up six help a developing country. If we can chairs. These chairs are provide affordable and quality healthcare provide it to the whole world.” occupied by professors to India, we can provide affordable from the best labs in the health-care to the entire world. That was go on. But if we set up large programmes world. They create teams in India with why I chose this field. and set ambitious goals, I find that larger whom they will remotely work ten groups can be created and it attracts more months in a year. Two months in a year What has been your learning in the money. Research is a bit open-ended. I am they will come to India and work past six or seven years about the state not saying that we will always get the re- together. Except now, because of COVID, of science in India? sults we need, but we have a better chance travel is restricted. The objective is to If I divide this into multiple parts, on of getting results. That is what I have create large teams in India. the quality of people I have no issue at been pushing for: to set ambitious goals. all. I believe we have as good scientists When the Centre for Brain Research If something comes up from these as anywhere in the world. Second is the was set up, I asked them, why don’t you projects, do we have the capacity to technology infrastructure. That can be address Alzheimer’s, Parkinson’s, Demen- translate that? fixed by investing enough money to build tia, ageing-related neurological disorders. I believe so. We have the world’s the technology infrastructure. And today, If we set such ambitious goals, I believe third-largest ecosystem for entrepreneur- we are seeing more and more money some of them will definitely be achieved. ship today. The number of unicorns is being invested into research. The whole increasing: India now has 50-55 unicorns. continuum, venture funding is available What was the state of research in these It is estimated to reach 100 in a couple more and more. The third is the system of areas when you entered? of years. I believe we have the ability research in India. What I learnt is that it This is a global problem. The entire world to translate this research. We are also is a mindset issue, an issue of us wanting is ageing, and India will also become an understanding what translation means, to do big and ambitious projects. Most of older society. There will be more people better. If you look at IIT Madras Research the research I found was small research, over the age of 35 than below. We are also Park, it is the best place to do research typically a professor with a couple of PhD living longer. One in five or one in six will and translation of research in terms of students, small budget, and they publish develop some kind of neurological disor- start-ups. Such endeavours are happening a paper, everybody is happy, and things ders. We have not found solutions globally in other research institutions. 7 44

SHAASTRA 2021 May-Jun 14.indd 44 5/18/21 7:27 PM SHAASTRA 2021 May-Jun 14.indd 45 5/18/21 7:27 PM ENVIRONMENT

VENIMO /123RF ZEROING IN ON

ZERO WASTE

Indian cities are harnessing technological interventions in the cause of solid waste management.

T.V. PADMA Hyderabad and Noida, diverted over 20,300 and beverage bottles, primarily PET (poly- million tons (MT) of waste from landfills. ethylene terephthalate) plastic, were mor- HE MOST visible symbols of It recycled 4,600 MT of dry waste and elec- phed into fabric and T-shirts; paper waste any modern city’s solid waste tronic waste; co-processed 8,400 MT of was recycled in paper mills; and low-grade management problems are its low-value waste, produced compost and plastic, mainly wrappers and other pack- overflowing – and overly odor- biogas from 6,800 MT of wet waste, there- aging material, found its way into alterna- iferous – garbage bins in pub- by reducing 37,000 MT of carbon dioxide tive fuel in cement kilns. lic places. However, for Wilma Rodrigues, (CO ) emissions. T 2 journalist-turned founder of Bengalu- The ‘zero waste’ concept is transform- INNOVATION TO THE FORE ru-based waste management company ing the informal waste-picking and resell- There are other such efforts to formalise Saahas Zero Waste, the smelly trash is a ing sector into an organised enterprise for the waste-picking sector with technical resource waiting to be recovered. She is some. In 2010, Hassan Khan, 26, was an competence. Hyderabad-based Banyan Na- on a mission to reuse almost all waste into informal waste worker, managing 6 MT of tion is applying innovation at every stage usable products, and she’s almost there, dry waste each month from open dumps, of the plastic recycling process: from the at 98%. “Over 90% of waste from homes, streets and purchases from other waste supply chain of discarded plastics to wash- offices, schools, and colleges can be recov- workers, on an illegally constructed facil- ing and making finished recycled pellets ered,” says Rodrigues. ity in Begur, Karnataka. He had 17 tempo- similar to virgin plastic. The concept of Zero Waste is gaining rary workers to assist him, in unsafe and Waste plastics come with accompanying traction the world over. The U.S. Environ- unhealthy conditions. labels, inks, prints and other remnants. mental protection Agency (EPA) defines it In August 2019, Khan partnered with Under the Banyan Nation system, infor- in somewhat verbose terms, but it can per- Saahas for four months under the latter’s mal collectors and waste aggregators are haps be summed up succinctly as abiding social inclusion project, which looks to trained to segregate the various kinds by the 3Rs: reduce, reuse, recycle. turn waste workers into entrepreneurs of of plastics. “Discarded plastics not only Between April 2019 and March 2020, Saa- sorts. The partnership saw Khan recycle contain contaminants, but are made from has, which also works in Chennai, Goa, dry waste into different products: water different types of resins,” notes Banyan 46

SHAASTRA 2021 May-Jun 14.indd 46 5/18/21 7:27 PM Rodrigues is on a mission to reuse almost all waste into usable products. And she’s almost there, at 98%!

Nation founder Mani Vajipey. His team has developed a data intelligence platform to map out the informal waste-picking sector in Hyderabad – collectors and aggregators – and has trained them to sort the materials. India, says Vajipey, has hundreds of thousands of informal waste recyclers, but the recycled products, including plastics, often have im- purities, and so they can only be converted into low-value applications such as bench- es, chairs, tables, buckets and mugs. For Saahas Zero Waste founder Wilma Rodrigues, smelly trash is a resource waiting to be recovered. Once segregated, the materials are taken through a series of washing steps in the ygen, the material does not burn, but the into biogas which can, in turn, be convert- company’s proprietary washing technolo- chemical substances in the biomass, such ed into electricity for street lighting or for gy, which yields a fine, high-quality pellet as cellulose, hemicellulose and lignin, poor households. Solid waste with high lig- that goes into mainstream products and decompose into combustible gases and nin content could be used for composting. packaging. These plastic granules are close charcoal. Simple pyrolysis produces bio- “We need to channel this compost to user to virgin quality products for mainstream oil, which is rich in oxygen and has a low groups such as farmers.” uses, including in fast moving consumer heating value; it is also highly viscous and goods companies and auto companies. “By cannot be mixed with conventional fuels. COVID AND WASTE eliminating contamination, we get pellets The oxygen content of bio-oil is typically The COVID-19 pandemic and the nation- of the quality we require,” says Vajipey. 35-40%, compared to 0.1-1.0% in petroleum. wide lockdown in 2020 have altered the dy- The process requires deep knowledge of However, when this decomposition is namics of waste collection and recycling. polymer chemistry and materials science. done under high-pressure hydrogen – a They have also impacted the quality of process known as ‘hydropyrolysis’ – it re- waste: there is now a higher proportion FROM WASTE TO FUEL sults in bio-oil with reduced oxygen. All of biomedical waste; and there has been a Recycling has caught the imagination of the remaining oxygen, as well as highly re- surge in packaging waste due to increased petrochemical giants too as a potential active substances, can be eliminated with online purchase of groceries. source of chemicals. An example is Royal a second-step ‘hydroconversion’ in which One of the lingering impacts is fear of Dutch Shell company, which partners with the complex molecules are broken down. contamination of recycled products, espe- companies in the U.S. to turn plastic waste Shell’s innovation is a catalyst that can, cially plastic and paper, says Brajesh Dubey, into chemicals that can be used to make fur- when combined with hydrogen at high tem- associate professor at the P.K. Sinha Centre niture, medical equipment, home applianc- peratures, break complex molecules in bio- for BioEnergy and Renewables, Depart- es and even smartphones. The company’s waste into those present in hydrocarbon fu- ment of Civil Engineering, Indian Institute global ambition is to make 1 million tons of els like petrol and diesel. India has a large of Technology, Kharagpur. People with mi- plastic waste in its chemical plants by 2025. biomass waste, and Shell’s technology has nor symptoms or those who are asymptom- While that technology is yet to come to the potential to convert all of these into atic also generate virus-laden waste such as India, Shell’s research and development drop-in transportation fuels, which can re- discarded masks, gloves and tissues. centre in Bengaluru has a demonstration duce India’s crude oil import dependency, Incineration or burning at high tem- plant to convert mixed waste (agricultural and also significantly lower greenhouse perature is one way to deal with biomed- waste and solid municipal waste) into fuel. gas emissions, the spokesperson claimed. ical waste. Other technological options It uses IH2 – ‘Integrated Hydropyrolysis and All this high tech is yet to come to India, include autoclaving, gas sterilisation, Hydroconversion’ – technology, which was but the country can manage efficiently chemical disinfection, microwave treat- conceived by U.S.-based Gas Technology In- proven technologies to handle solid waste, ment, irradiation and thermal inactiva- stitute (GTI) and developed in collaboration says T.V. Ramachandra, professor at the tion. But Indian waste is inherently ‘wet’, with Shell Catalysts & Technologies. Centre for Ecological Sciences at the Indi- given the high amount of water in organic “We are seeking to prove that forestry an Institute of Science (IISc), Bengaluru. or food content, which reduces its net calo- waste or woody biomass; agricultural res- “The latest techniques developed else- rific value. “Waste-to-energy incineration idues such as bagasse and straw; and oth- where are energy-intensive and not suit- plants in India are struggling” to cope with er wastes such as sorted municipal solid able for Indian wastes” which have a high the low calorific value, says Dubey. waste can be converted into lower carbon proportion of organic material, he notes. An emerging technology is ‘hydrother- (typically around 70%) transportation fu- “Solid waste generated in Indian house- mal carbonisation’, a kind of autoclav- els, including petrol, diesel and jet-fuel on holds is predominantly organic, and con- ing at high pressure and temperature, in a commercial scale,” says a Shell spokes- verting this component to biogas for en- which the moisture content of waste does person. “We have proven that IH2 can work ergy or compost would be the best,” says not pose a major problem. The technology on a pilot scale and the technology is now Ramachandra. It would also provide jobs can yield hydrochar, a carbon-rich materi- in demonstration phase.” to unemployed youth, he adds. al that can be used to improve soil fertility Simply put, during pyrolysis, organic Ramachandra says that solid waste with or even sequester carbon and reduce the material such as biomass is heated in the a higher proportion of food leftovers and GHG effect. Other spin-offs of the technol- absence of oxygen. Because there is no ox- other organic fractions can be converted ogy include activated carbon and energy 47

SHAASTRA 2021 May-Jun 14.indd 47 5/18/21 7:28 PM ENVIRONMENT

Banyan Nation has developed a data intelligence platform to map out the informal waste-picking sector.

conditions; else, endogenous heat must be applied prior to the use of heat, such as a bio-drying process in which organic matter is decomposed and dried by generated heat using a biological reaction. One such MBT facility exists in Nashik in Maharashtra. It was first introduced as a mechanical process to produce RDF, as well as compost for agriculture. It now treats 500 tons of mixed domestic waste daily to produce 20 tons of RDF as a fluff Banyan Nation founder Mani Vajipey, which is further processed to form pellets whose team applies innovation at every and also produce the ‘digestate’ or a nu- or briquettes for use in industries and stage of the plastic recycling process. trient-rich substance that can be used as power plants. The city plans to increase a fertiliser; and a stable, organic ‘Com- the capacity to 80-100 tons a day. Similarly, storage for batteries. Dubey’s team at IIT post-like Output’ (CLO). Both the digestate a ‘Waste to Energy Plant’ in Ghazipur in Kharagpur has set up a pilot hydrothermal and CLO have potential use as a source of Delhi aims to generate 12 MW of electric carbonisation plant and is trying to pro- organic matter on land or to restore land- power, using 1,300 tonnes of municipal sol- mote the uptake of its byproducts. fill caps and can also be repurposed as con- id waste per day. Non-government organisations such as struction materials. Saahas and Banyan, global energy giants Some of the high-calorific value, com- SCIENTIFIC LANDFILLS such as Shell and elite institutes such as bustible contents of the municipal solid While changes in waste management are the Indian Institute of Technology Bom- waste can also be converted into a fuel, afoot in Indian cities, landfills won’t dis- bay are all working on India’s mounting called ‘refuse derived fuel’ (RDF) that can appear overnight. One option, says Ajay problems of solid waste, and waste recov- be burnt easily in a combustion boiler. To Nagpure, researcher at the World Resourc- ery and recycling into a range of products, make RDF, the waste must be shredded and es Institute Ross Center, New Delhi, is to from biogas and fuel, to plastics and fabric sorted to remove all non-combustible ma- construct ‘scientific landfills’ designed to is the current preference. An IIT Bombay terial. The combustible portion is formed minimise the impact on land, soil and water study noted that “an integrated municipal into pellets, which can be sold as fuel. RDF through seepage; and air through burning solid waste management approach with a can be used in specially designed power of waste. They also allow recovery of meth- mix of recycling, composting, anaerobic plants that can use this form of a fuel, or ane generated from decomposition of the digestion and landfill had the lowest over- mixed with biomass waste and burned in waste, which can be used to generate energy. all environmental impact.” Uncontrolled power plants. In the U.S. and elsewhere, a third of dumpsites are causing environment chal- A second fuel is ‘solid recovered fuel’ landfills have landfill gas recovery sys- lenges, the researchers say. (SRF), made from a mixture of the biolog- tems’; a quarter more are good candidates Scientists from IIT Bombay’s Centre for ic-origin waste such as paper, cardboard, tex- for this system, he says. Such a system dis- Environmental Science and Engineering tiles and wood; and plastics and foils. These poses of solid waste, recovers energy, and studied the life-cycle of waste manage- components are mechanically sorted out, reduces greenhouse gas emissions. “This ment under six scenarios that could serve dried and biologically treated to form SRF system has multiple benefits, and I feel In- as alternatives to open dumping. These produced in the form of bales, fluff or hard dia should try to develop it.” include landfills with biogas collection, in- and soft pellets. It is of use as a coal substi- Several cities such as Indore, Pune and cineration, and different combinations of tute in cement, lime and steel industries. Surat are turning to information tech- recycling, landfill, composting, anaerobic The initial MBT facilities were devel- nology in this cause: for instance, ‘smart digestion and incineration. oped to reduce the environmental impact garbage monitoring’ technology uses the of landfilling residual waste in Europe. Global System of Mobile (GSM), an in- BEYOND LANDFILLS But it is increasingly being considered as fra-red sensor or LEDs to indicate when All these efforts reflect a new thinking to a suitable option in cities in Asia, which the dustbin is filled to a specific level, at an old problem. Each year India generates have mixed, and often unsorted, munic- which point the compaction module actu- 63 million tons of waste. Indian cities have ipal waste, often with fewer recyclables. ates and compresses the waste. traditionally relied on unhealthy solutions The technology can be localised, uses less When the garbage reaches a certain of landfills and/or open burning of waste energy, does not need high-end machines, level, the bin’s location is displayed via Wi- without the use of incinerators. and can be integrated with other waste Fi and GSM on a centralised web server, Several international environment management technologies. which helps municipal authorities coor- agencies suggest Mechanical-Biological Waste such as food waste or inedible dinate the collection. And in 2020, Hyder- Treatment (MBT), a pre-treatment method parts of fruits or vegetables has high levels abad introduced 55 advanced compactors before landfilling to reduce the amount of of moisture and organic matter. The intro- for garbage collection and transportation. waste. MBT involves mechanical crushing duction of such waste into the MBT pro- “Indian cities are trying their best to and sorting (to recover recyclable materi- cess may result in poor crushing and sort- adopt new technologies, but they still need als), followed by biological treatment such ing efficiency. The moisture content must to work to implement new technologies by as aerobic and anaerobic decomposition. be lowered before the start of the MBT pro- focussing on capacity development,” says Anaerobic digestion can recover biogas, cess. Solar drying is possible under some Nagpure. 7 48

SHAASTRA 2021 May-Jun 14.indd 48 5/18/21 7:28 PM SHAASTRA 2021 May-Jun 14.indd 49 5/18/21 7:28 PM CLIMATE SCIENCE

PHOTOS: NIDHEESH M.K.

A KERALA VILLAGE SHOWS THE WAY Harnessing technology, and drawing on enlightened ecological policies, Meenangadi in Wayanad district is on the path to becoming India’s first carbon-neutral village.

NIDHEESH M.K. Yet, Meenangadi, a foggy hill station presented a paper at the United Nations in arguably one of the greenest places in Climate Change Conference in Paris. Rep- N THE faint light of January, there’s Kerala, has set itself an ambitious goal: resentatives from Thanal, a non-profit or- a quaint twinkle in Madhavan P.K.’s to reverse the impact of climate change ganisation that works on environmental eyes, but it masks a deep concern. As by becoming India’s first carbon-neutral projects in Kerala, attended the session. the 83-year-old coffee farmer glides village by 2027. And it is halfway towards Inspired by the conference proceedings, through his farmland of less than getting there by harnessing an unusual they envisioned a carbon-neutral village Ian acre in Meenangadi village in Kerala’s experiment, which has put it on the global in Kerala. Wayanad district, he caresses a pretty un- ecological map. That thought experiment acquired life usual coffee bush: it has both unharvested India is the third-largest emitter of in 2016, when a Communist Party of India beans and white flowers. “Normally, the greenhouse gases, behind the United (Marxist)-led government came to power beans from the plant would all have been States and China (excluding the European in Kerala, and Isaac became Finance Min- harvested before the flowering season be- Union as a single block). A decade of rap- ister. gins,” he says. “But it’s all changed now: id economic growth, which transformed Wayanad, being small and climate-sensi- winter is arriving later than before, and is villages into urban metropolises, is large- tive, was seen as the best place for the pilot rushing prematurely into spring.” ly to blame, according a study published scheme. Meenangadi panchayat was cho- That seasonal shift has had serious eco- last year in Economic and Political Weekly. sen since the CPI (M) had an overwhelm- nomic consequences for Madhavan. Over India’s capacity to bend the arc of those ing majority there, and it was easier to get the past decade, the coffee yield from his emissions will hinge on the future of In- things going. farm has fallen to a third. “It’s the cli- dian cities as well as its villages. And if But as Isaac points out, the plans expand mate,” he explains. “It’s either too hot or Meenangadi’s ecological experiment suc- way beyond just that one village. “Once the too cold these days.” ceeds, it could serve as a model for how pilot project (at Meenangadi) is on track, For countless farmers like Madhavan, greenhouse gas emissions can be reduced we want to expand it across all of Wayanad the ravages of climate change impose without compromising on development. district,” he said. Nor is this campaign real-world costs. Most of Meenangadi’s motivated by just feel-good idealism. “We 30,000 residents are subsistence farmers: HOW THE JOURNEY BEGAN want to brand the coffee from Wayanad as they grow crops and raise livestock for The village’s journey on the low carbon coming from a carbon-neutral place and their own use. But they are at the mercy path began quite by chance. In 2015, de- provide a better return for farmers.” of everyone from rain gods to politicians. velopmental economist Thomas Isaac It is impossible for a village to have 50

SHAASTRA 2021 May-Jun 14.indd 50 5/18/21 7:28 PM zero carbon emissions. However, cut, the proceeds from the timber villages can reduce their carbon sale can more than repay the loan. footprint, and offset their emis- There was one problem, though: sions – by planting trees, for in- financial regulation in India does stance. But almost five years in, not cover loans against trees. But Meenangadi’s ‘climate science’ villagers found a work-around experiment shows that building business model. They created a carbon-neutral future is more a an escrow mechanism using a political challenge than a techno- `10-crore budgetary support that logical one. Isaac provided. The money was For a start, no data about emis- deposited in a Fixed Deposit with sion levels was available, said Ajit a local cooperative bank, which is Tomy, who quit his engineering typically run by grassroots lead- job to head Thanal’s data col- ers. The ‘tree bank’ loans are dis- lection exercise in Meenangadi. bursed from the FD interest. With the help of hundreds of stu- This model gives farmers an in- dent volunteers, Thanal extracted centive to let the trees survive for and analysed data from various years, which allows the carbon to official departments to estimate be sequestered for longer periods the total emissions, he said. in the tree as well as in the soil “For example, we would get data biomass. Esablishing a cash flow on energy consumption (which from the trees also ensure that contributes to indirect emissions) villagers are not forced to bear from the State electricity board,” the burden of opportunity cost on he said. But only a sample house their upkeep. survey could establish the extent of emission from firewood burn- THE WAYANAD MODEL ing for domestic cooking (which Farmers are already Across the State border, in Ko- contributes to direct emission). paying the price of climate dagu, Karnataka, a contrasting Similarly, estimating the amount scenario presents itself. Kodagu of carbon sequestered required change: over the past is contiguous with Wayanad, and data on tree population; in its both places have a similar ecosys- absence, Thanal had to count the decade, coffee yields have tem. Kodagu’s coffee estates are trees in every home. fallen to a third due to rich in biodiversity, just like in These data sets were codified Wayanad, and service a number in a 2017 report. It estimated the seasonal swings. of ecosystems such as bird species total emission of GHGs (Green- and microclimate. But in Kodagu, House Gases) in Meenangadi for the protection mechanism works

2016-17 at 33,375 CO2eq (carbon “This whole place was once a filthy by a top-down legal approach. dioxide equivalent, a unit that measures dumpyard,” said Paulson P.A., who has There, trees belong to the government, the environment impact of one tonne of been driving the village’s waste truck for and are protected by law: the estate own- GHG in comparison to the impact of one 24 years. “Some households unwilling ers are not allowed to cut them. However, tonne of carbon dioxide). The transport to pay to have their garbage taken away coffee estate owners often find themselves and energy sectors contributed the most would burn it. But now, we have more spending on labour to maintain the shade (45% and 39%, respectively), followed by waste than we can process.” cover for their coffee plants. Over the de- waste management, agriculture and for- cades, since farmers are not incentivised estry sectors. MONEY GROWS ON TREES! to “protect” the trees, they have moved to Next came the ‘carbon balancing’ part, Meenangadi’s most ambitious, and argu- monoculture plantations of silver oak, a which involved getting people to change ably the most daunting, target is else- recent study from Bengaluru-based Asho- their habits to pollute less and plant more where: to plant five lakh trees, the number ka Trust for Research in Ecology and the trees. The local government sought to required (in experts’ reckoning) to cancel Environment (ATREE) established. make coffee farmers aware of the crop out current emission rates. To secure vil- Silver oaks have the kind of tree planks losses they would face from an increase in lagers’ support for this initiative, Isaac that allow coffee plants to grow in the shade. temperatures, by an estimated 2-4 degrees and his colleagues developed a financial Lopping off the extra branches to maintain over 25 years. It also streamlined sectors instrument, locally known as ‘tree bank’: the right ‘shape’ does not entail excessive within its direct influence, such as waste farmers are given interest-free loans of `50 labour costs. And silver oaks have good tim- management. a year for every tree they plant. Only after ber value when they are cut, which gives ‘Zero waste and Zero Emission’ is one a minimum of three years of tree-planting farmers an alternative source of income. of the pillars of the Meenangadi project. can farmers avail of the loan. And the loan However, the study noted, silver oaks are Although waste accounts for only 3% of needs to be repaid only when the trees are less welcoming to biodiversity. Similarly, village emissions, the administration cut, which is an incentive not to cut them in northern Karnataka, farmers have tak- reckoned there was scope for reducing this in the short term. en to growing eucalyptus: they can sell the almost entirely. The results are already The saplings to be planted are chosen timber for paper. But the trees suck up an showing up: once-ubiquitous plastic cov- for their environmental suitability, and extraordinary amount of groundwater. ers have nearly disappeared, villagers say. geo-tagged by a state-run nursery. Some In Wayanad, however, the farmers not Garbage burning is penalised; the waste is are planted in public places; for instance, only have a personal incentive to grow the segregated and collected at a common fa- 38 acres of barren land belonging to an old trees, but the trees have been well chosen cility, from where the reusable waste goes village temple has been reforested. Others by the State government so that they are into making manure, and plastic waste is are chosen for their commercial utility for aligned with the social and environmental used in road construction. farmers so that when the tree is eventually benefits for the area. 51

SHAASTRA 2021 May-Jun 14.indd 51 5/18/21 7:28 PM CLIMATE SCIENCE

The success of the Wayanad model lies preneurs looks to turn in its fusing of environmental goals with the agrarian ‘waste- behavioural economics. The government is lands’ into tourist con- not explicitly telling people what to do, but structions — it is getting is nudging them towards an optimal choice. warmer. “When I came One downside, though, of such a strategy here first, just four years is that there is little to stop farmers from ago, I needed a sweater cutting the trees if they are offered higher to keep warm in Janu- incentives for such a choice. They are not ary,” recalled Ajit. “Now, morally bound to follow this path unless I can’t bear the heat in they are effectively, emotionally attached. January.” Already, there are signs of that. This is true elsewhere Elections to local bodies across Kera- in Kerala, and more so la were held in December 2020, and the in ecologically fragile Congress, the CPI (M)’s political rival, se- places like Wayanad, cured a majority in the Meenangadi pan- experts point out. A gov- chayat. There is already speculation that ernment study noted the Wayanad climate-neutral project may that between between go into a limbo if the new administration 1981 and 2016, only in disfavours it. four years had the State experienced a “nor- COMPETING PRESSURES ON LAND mal” monsoon. Errat- There is also a real estate boom across ic rains are resulting Wayanad owing to a new generation of in rain bombs like the entrepreneurs tapping into the tourism megafloods of 2018, or potential of the scenic hills. Some farmers the drought in 2017, the reckon that selling a portion of their land worst in a century. More to feed this construction boom will yield generally, Kerala strug- better returns than farming offers. Mad- gles for freshwater, says havan’s son, for instance, has sold a part of Dineshan V.P., scientist the family’s farmland, even going against and faculty at the Cen- his father’s wishes. “But I want to contin- tral Water Resources ue farming – if not for huge returns, at Development and Man- least to ensure my family’s sustenance,” agement (CWRDM), a says Madhavan. government-run water Providing farmers longer-term incen- studies entity. tives could help, reasons Ulka Kelkar, Di- Kerala boasts of 44 rector of Climate Change at global climate rivers, but that is a mis- research outfit World Resources Institute leading bit of statistic, Farmers like Madhavan can India. The government, she says, is right he says. Going by na- to market the coffee from Meenangadi in tionally accepted defi- secure an interest-free loan of the global market by branding its origin in nitions, major rivers `50 a year for every tree they a carbon-neutral place. should have a catchment A number of countries, and even compa- area of 20,000 sq km; on plant. nies, are committing themselves to net-ze- that count, Kerala has ro emissions in a few decades, Kelkar none. It has four median rivers of 2,000- Many other cities – in India and around points out. Meenangadi’s farmers can ben- 20,000 sq km; the rest are smaller than that. the world – are carrying out similar eco- efit from such initiatives, she adds. “In fact, the State’s natural conservation logical experiments as Meenangadi, For now, farmers have largely welcomed systems have failed to an extent that the points out Kelkar. For instance, Indore, the climate-neutral initiative. Madhavan official machinery has to provide tanker in Madhya Pradesh, is drawing up plans was beaming when we met in January: he water in ecologically fragile areas nearly to become carbon-neutral. Similar plans had just received `5,000 for planting a hun- every summer,” he says. have been unveiled for the Union Terri- dred trees under the ‘tree bank’ scheme. Most Indian States are similarly wracked tory of Ladakh. The Sikkim government There is an element of self-interest in what by the ravages of climate change. Which is is looking to bring the entire State under farmers are doing, Madhavan acknowledg- perhaps what gives Meenangadi’s ecologi- organic cultivation; Pune has a ‘climate es, but it is not all. cal experiment a heightened relevance for action plan’ centred around a low-carbon other Indian cities and villages. pathway; and Andhra Pradesh is talking REALITY OF CLIMATE CHANGE Meenangadi is a metaphor for all Indian of smart villages. They will all be looking Places like Wayanad top the list of climate villages, where the emphasis is on develop- keenly for lessons from the experiment un- change hotspots in India. For farmers, cli- ment, and all small towns that are growing der way in Meenangadi village. mate change, and the risk of flooding or and becoming bigger, says Kelkar. The de- Back in the village, as Madhavan saun- drought, are already part of day-to-day re- cision they have to make is stark. “Do you ters around his farmland, there is a dis- ality, notes Madhavan. They may not know want to choose a high-carbon pathway that cernible spring in his step. The prema- FOR PRODUCT INFORMATION AND CAPABILITY PROFILE, CONTACT: the exact science behind it, but it is part of locks you into a certain kind of infrastruc- turely blossoming white flowers on the their lived experience, he adds. ture and investment for decades? Or will coffee bushes, which bear testimony to the Asia / Headquaters San Antonio Yardley, PA USA Stuttgart, Germany Shanghai, P R China There is widespread awareness in you choose an alternative set of technol- ravages of climate change, are of course US Production Plant Wayanad that as the district develops — ei- ogies and infrastructure and investment, a source of concern. But in Meenangadi, Production Plant ther as a service economy that caters to a which is not only good for the global cli- that concern is contrasted somewhat by [email protected] [email protected] [email protected] [email protected] [email protected] widely used National Highway that passes mate, but alsok for the local environment the hope inspired by a hundred trees plant- +91 80 2204 8800 +1 210-467-5119 +1 609-651-8238 +49 711-65500242 +86-15-001803724 through it, or as a generation of new entre- and the health of the people?” ed afresh on the same farmland. 7 ISO 9001:2015, IATF 16949:2016, ISO 13485:2016, AS 9001:2016, ISO 14001:2015, ISO 45001:2018, NADCAP Certified 52

SHAASTRA 2021 May-Jun 14.indd 52 5/18/21 7:28 PM FOR PRODUCT INFORMATION AND CAPABILITY PROFILE, CONTACT:

Asia / Headquaters San Antonio Yardley, PA USA Stuttgart, Germany Shanghai, P R China Production Plant US Production Plant [email protected] [email protected] [email protected] [email protected] [email protected] +91 80 2204 8800 +1 210-467-5119 +1 609-651-8238 +49 711-65500242 +86-15-001803724

ISO 9001:2015, IATF 16949:2016, ISO 13485:2016, AS 9001:2016, ISO 14001:2015, ISO 45001:2018, NADCAP Certified

SHAASTRA 2021 May-Jun 14.indd 53 5/18/21 7:28 PM BOOKS A marketplace for moonshots ©GILOLA CHISTE Mariana Mazzucato makes a compelling case for reimagining governments and economic systems, to spur innovation and face up to tomorrow’s challenges.

A.K. BHATTACHARYA encourages privatisation or outsourcing of functions it HE outbreak of COVID-19 should have discharged on its Thas seen governments in dif- own. This can degenerate into ferent countries adopt different a vicious cycle. It leads to lower approaches to tackle the pan- investment in public facilities demic. Success in controlling and capabilities, institutional the pandemic has not been easy weaknesses and an increased to achieve. Many rich countries dependence on private consult- simply could not cope with the ing companies. Thus, the abil- pressures of managing the pan- ity of many governments has demic, while some developing suffered hugely in dealing with countries, such as Vietnam, COVID-19. have handled it rather well. How did the rich countries fail? STATE CAPACITY IS THE KEY Mariana Mazzucato, a It is this belief of Mazzucato well-regarded economist, has that acts as the central prem- Mazzucato favours transforming governments an explanation. Her belief is ise of her latest book, Mission that handling the pandemic has Economy: A Moonshot Guide to and strengthening their systems for health, not been a question of resourc- Changing Capitalism. Taking education, transport and the environment, in the management of COVID-19 as order to give the economy a fresh impetus. an example, she argues that government intervention in times of crises yields the desired re- tion, transport and the environ- markets people wanted, rather sults only if the state has the ment, and thereby giving the than fixing the problem in mar- necessary capability to make economy a fresh impetus and kets. The focus in a mission a difference. But governments direction. This is not to be con- approach has to be on identify- in most countries have reduced fused with the desire, often ex- ing the goals and how budgets themselves to being “fixers of pressed by Left thinkers, for a could be structured to achieve market failure” at best – and bigger and larger government. those goals. The lessons from “outsourcers” at worst. It is a desire for a government the Apollo Mission are many, Instead, Mazzucato believes that needs to build capacity to and Mazzucato devotes an en- that governments should in- face up to the new challenges. tire chapter to discuss them vest in building capacity in and, in particular, underline Mission Economy: key areas such as “productive THE ORIGINAL ‘MOONSHOT’ the importance of vision and A Moonshot Guide to Changing capacity, procurement capa- The inspiration for her purposeful leadership, risk-tak- Capitalism — Mariana Mazzucato bilities, public-private collab- thoughts on reimagining gov- ing innovation, agility and flex- Penguin Books orations that genuinely serve ernment is triggered by a de- ibility in bringing about organ- Pages 245+XXIV | Paperback the public interest, and digital velopment in the United States isational change, collaboration ` 799 and data expertise (while safe- more than half a century ago. and outcome-based budgeting. guarding privacy and securi- Mazzucato draws upon the les- es. Instead, success has crucial- ty)”. If the government does sons from a project that the U.S. RETHINKING CAPITALISM ly depended on the depth and ro- not build such capacity, the Government had in 1962, under It is important to recognise that bustness of the organisational prospects are scary. Compa- President Kennedy, embarked Mazzucato is not just trying to capacity of the government and nies that are brought in to do on to send a man on the moon rethink the way governments its ability to engage with pub- the government’s job would before the end of that decade. should function; she is rethink- lic-private partnerships. Quite capture the agenda and public This was the Apollo Moon ing capitalism itself. The two to the contrary, however, the cause would be in jeopardy. project and it was not about are inextricably interlinked. developed world has embraced The sombre thought that outsourcing or privatisation. It Capitalism could be changed an ideology that has allowed Mazzucato’s analysis triggers was about public-private part- by modifying how governments the government to take a back is that governments in most nership. Most importantly, it are structured and how busi- seat and intervene occasionally countries have made a serious was about a mission approach – nesses are run and how public or selectively to fix problems as mistake in weakening them- a strategy that involved design- and private entities can collab- and when they arose. selves even as they face a pleth- ing policies that could channel orate to achieve pre-determined This is what has inspired ora of challenges on health, investment, innovation and goals. Such focus on rethink- the new public management climate and digital technology. collaboration to achieve the de- ing governance structures is principles adopted by most She makes a passionate plea sired goals. an integral part of the kind of developed countries. In such for transforming government More significantly, this was mission-oriented approach that a scenario, the government from within and strengthening a strategy that required gov- Mazzucato advocates to address withdraws itself, even as it its systems for health, educa- ernments to ask what kind of the global economic challenges. 54

SHAASTRA 2021 May-Jun 14.indd 54 5/18/21 7:28 PM ©THISSATAN KOTIRAT/123RF.COM A ‘moonshot’ project needs a mission approach, a strategy that involves designing policies that can channel investment, innovation and collaboration to achieve the goal.

failure. Instead, she argues, government investments can crowd in private investments, when these are structured stra- tegically. An equally popular idea, which she dismisses, is that governments need to run like businesses. She also questions the ideas that outsourcing saves taxpayer money and low- ers risk and that governments should not pick winners. All these ideas are a product of neo-liberal economic thinking, and Mazzucato challenges An entire chapter in the announce far too easily and fre- are benefits for investing short- them in detail with examples book, therefore, is focussed on quently. This process implicitly term more attractive than those and anecdotes. the crisis that Mazzucato be- incentivises the FIRE sector for investing long-term? Many There is an excellent section lieves has gripped capitalism. players to continue to take ex- of these questions have been on the changes that Mazzuca- Her gripping analysis brings cessive risks. raised in the past. But Mazzu- to believes must be brought out how instead of ensuring a cato scores by placing them in about to strengthen the struc- sustainable growth path, cap- THE CURSE OF SHORT-TERMISM the context of a general need ture of political economy that italism has widened inequal- Similarly, business has begun for reimagining the govern- governments try to manage ities by making the rich even excessively focussing on quar- ment with “the capacity and in different countries. There more rich and created specu- terly returns to shareholders, capability to energise and ca- can be little debate over the at- lative bubbles. Private debt instead of genuine growth of talyse the economy to be more tention that she believes must rose to 150% of gross domestic the companies. Such pursuit purpose-driven”. be focussed on how business, product (GDP) in the US, 170% of shareholder value has en- government and civil society in the UK, and 200% in France; couraged companies to devise MAZZUCATO THE MYTHBUSTER should work together to cre- and if you thought the Chinese financial structures that bene- In that process, she also busts ate value, the need for govern- economy was an oasis of sorts, fit shareholders more than the five popular myths about the ments co-creating and co-shap- Mazzucato will quickly remind other equally important stake- government and business – ing markets, instead of fixing you that private debt in China holders like workers, suppliers, and the manner in which they market failures, organisations is now 207% of GDP. customers and most important- operate. The idea that busi- built on the principle of co-op- With amazing clarity, Mazzu- ly the society in general. The nesses create value and take eration and not competition, cato explains how capitalism lack of focus on climate con- risks, while governments only a renewed emphasis on long- has been embroiled in its cur- cerns and the abdication of re- de-risk and facilitate, is com- term financing and the goals of rent crisis. She identifies four sponsibilities by governments prehensively debunked. Citing distribution, inclusive growth, sources of the crisis that faces in fixing economic problems the work done by the National partnership and participation. capitalism: short-termism of have underlined the need for a Aeronautics and Space Admin- A big attraction of the book the financial sector, financialisa- new approach. istration (NASA), the Defence is that Mazzucato does not tion of business, climate emer- Thus, Mazzucato argues that Advanced Research Projects write like an economist. A gency, and absent governments. governments must reinvent Agency (DARPA) and the Euro- simple style, to the extent that There can be no quarrels with themselves to provide direction pean Organisation for Nuclear she avoids using jargon, makes her diagnosis of the problem. to its policies on taxation, fiscal Research or CERN, Mazzucato the book accessible and easy There is also no denying that management or even the con- establishes that governments to read. You may not agree the financial sector has been duct of monetary policy. She do create value and take risks. with her entire thesis or may largely financing itself or the raises a few important ques- Indeed, the ambitious public even debunk it as utopian, but FIRE sector (companies in the tions: Why is there no attempt investment in the areas where her plea for reinventing the fields of finance, insurance and towards de-financialisation or NASA, DARPA and CERN op- government to tackle the chal- real estate). The problem gets sustainability? Why is there no erated helped create opportu- lenges that the global economy more complicated, as she notes, attempt at taxing the environ- nities for the private sector to faces is compelling. 7 when FIRE profits remain pri- mental “bads” and favouring expand and grow. A.K. Bhattacharya vate, but its losses become pub- “green”? Why are capital gains Mazzucato also debunks Editorial Director, lic as a result of the bailout of taxed at a rate lower than in- the notion that the purpose of Business Standard these sectors that governments come earned from work? Why government is to fix market @AshokAkaybee 55

SHAASTRA 2021 May-Jun 14.indd 55 5/18/21 7:28 PM BOOKS Waiter, there’s a chemist in the kitchen! An appetising book that uses the tools of modern science to document Indian culinary traditions.

SAMAR HALARNKAR MasterChef Australia, a cluding us, radiates wildly popular televised some energy, but it is S SOMEONE who has been competition of home not enough to cook food. Acooking for more than 30 chefs, and I am not a big “But if the object in years, here are a few things I fan of cookbooks, al- question is reactor num- did not know before I read this though I possess nearly ber 4 at Chernobyl,” he book but am glad I do now. 100. observes, “the results That hard-to-digest carbo- So, to get me inter- are not pretty.” hydrates proliferate in rajma, ested in a book that de- Ashok casts new light which become food for gut constructs the science on everyday Indian cook- bacteria who convert it to gas of Indian cooking is no ing. He recommends we (the flatulence is good, since mean feat. As a former use spice powders in it spurs the growth of healthy science writer, I do con- good time before they gut bacteria). That marination fess to more than a pass- turn to “flavourless sand does not penetrate beyond the ing interest behind the (hint: use a spice or cof- surface of meat, but brining science of anything, but fee grinder to make spice does, improving flavour and this book is meant to be powders when you need preventing the loss of wa- many things to many The food science in them). There is a long ter from muscle tissue. That people. It is a guide to the home the book is excellently analysis of whole spices and the key to using and under- chef, with tips to improve basic blends and lengthy expositions standing yoghurt in a gravy skills, such as browning onions deconstructed, but it on the science of sugar, salt is to whisk in some starch to or using a pressure cooker bet- could still get some- and flavour. His oeuvre is vast strengthen the emulsion so ter. It is a lure to the scientist to what overwhelming and includes the science be- it does not break down when explore the joy of food beyond hind using yoghurt, tamarind, heated. the science. And it hopes to be for the lay reader who mango, vinegar and tomato. of interest to the lay reader in- cooks. terested in good writing. THE SMELL TEST I liked the fact that Krish I also found most fascinating Ashok says the book will not Since Ashok favours — and his exposition on orthonasal make you a chef but a better makes a strong argument for — olfaction, or what you smell be- home cook, which indeed is transforming cooking into an fore you eat, which is quite dif- what I am. engineering discipline, “one ferent from the taste, which is Ashok’s central argument with standardised methods why cheese may smell strange, is to “dexoticise” Indian food, and a finite set of easy-to-re- flame-roasted brinjal may use “the tools and language member general principles smell acrid and metallic and – of modern science and engi- that work for all kinds of dish- my favourite – dried fish, may neering” to analyse and docu- es”, his reductive culinary smell extremely fishy. ment myriad Indian culinary philosophy is: “Cooking is ulti- The book abounds in handy traditions. By not doing so, he mately chemical engineering.” cooking tips: for the best fla- writes, we are doing the “food This is both the book’s vour, brown ingredients before Masala Lab: equivalent of lip-synching to a strength and weakness. The adding them to gravies; use a The Science of Indian Cooking pre-recorded track”. food science he writes about batter of maida, salt and vodka — Krish Ashok is excellently collected and for pakoras (alcohol reduces Penguin DEMYSTIFYING THE DAL deconstructed, but it could get gluten development, stops sur- Pages 280 | Paperback Unlike Western cooking, somewhat overwhelming for face starches from absorbing ` 399 writes Ashok, Indian cuisine his major target audience: the too much water, making pa- suffers from a historical lack lay reader who cooks. koras crisper); use a pinch of The daily act of cooking of record-keeping and, subse- We learn about the basic baking soda to brown potatoes, food is, of course, intrinsic quently, standardisation. “Art physics of heat, density, air blanch green vegetables, tende- to our survival. But since hu- is and should be hard to mas- pressure, conduction, convec- rise tough meat, make fluffier mans are no longer simple ter, but if the craft is hard to tion, radiation, denaturation omelettes and browner dosas. hunter-gatherers, it is, to the get right, then the documenta- and — most importantly for He has “algorithms” for soft interwoven community of Ins- tion is pretty inadequate… By the Indian cook — the Mail- chapatis and perfect idli/dosa tagrammed modern mankind, treating our culinary tradition lard reaction, which explains batter. so much more. Cooking now as something sacred, artistic the browning of food. There is Science, in other words, in encompasses the culinary arts, and borderline spiritual, we a whole chapter on the science the service of breakfast, lunch, science, tradition, pleasure are doing it a great disservice.” and techniques of browning dinner — and everything in be- and intuition. He uses Western music as a and caramelisation of onions, tween. 7 I am given over mainly to metaphor for the power of sim- garlic, cabbage and potatoes, Samar Halarnkar is a part- the last, cooking as I have all ple visual notation “that is able written with verve and humour. time journalist, part-time cook, these year by my wits more to accurately capture every nu- For instance, he explains full-time father and the author than reason, turning out food ance” and explains why you how a hot light source gener- of A Married Man’s Guide to for my family through trial and can play a Bach concerto as the ates infrared radiation to cook Creative Cooking (And Other practice. I write a bi-monthly great composer himself did in food, as with a shawarma. Dubious Adventures). cooking column, I do not watch the 18th century. Technically, everything, in- @samar11 56

SHAASTRA 2021 May-Jun 14.indd 56 5/18/21 7:28 PM SHAASTRA 2021 May-Jun 14.indd 57 5/18/21 7:28 PM BOOKS

©UNIVERSITY OF OXFORD From whence we came Part-travelogue, part-forensic genomics, Higham’s book gets us better acquainted with our anthropological ancestry.

SRINATH PERUR ple to explain this than Tom Higham. As Professor of Ar- HE YEAR 2010 was a big one chaeological Science at Oxford Tfor reckoning with our ori- University and Director of the gins as a species. This was the Oxford Radiocarbon Acceler- year in which it became clear ator Unit, he has been directly that Neanderthals, long stereo- involved with many of these typed as a somewhat brutish recent revelations. The World sort of extinct human, had in- Before Us sometimes reads terbred with us and contributed like a travelogue, as we ac- some DNA to almost everyone company Higham to locations today who lives outside Africa. with archaeological sites – a This was also the year in which Malaysian rainforest, the Al- a previously unknown group of tai mountains, a Parisian mu- archaic humans – later named seum, Israel, Beirut. At other the Denisovans – was identified times, it reads like an early by obtaining ancient DNA from archaeologist’s account, with Higham introduces us to the scientific advances a bone fragment found in a Si- plot twists arising from depos- berian cave. Since then, it has its being out of sequence. But that are complementing traditional archaeology become clear that fossils found mostly, it introduces the read- and paleo-anthropology, and yielding in South-East Asia come from er to the scientific advances information from tiny slivers. two more groups of archaic hu- that are now complementing mans. It now seems likely that traditional archaeology and at least five distinctly different palaeo-anthropology – and ing revolution in DNA sequenc- The Denisova cave in Si- human species were walking yielding mind-bogglingly rich ing technology has led to data- beria, where the girl’s bone information from the tiniest of bases of modern genomes from sample came from, has yielded slivers. across the world. Comparing thousands of bone fragments, Take, for example, what we DNA from the Denisovan sam- many chewed up over the mil- now know about the Deniso- ple with that of modern hu- lennia by hyaenas or bears. vans. Unlike the Neanderthals, mans revealed that the groups Most are not human, but with who turned up copiously as had interbred, and people now so few Denisovan samples, skulls and skeletons beginning living on the Pacific islands it was vital to try and find in the mid-nineteenth centu- in the region of Papua New human bones among them. ry, there exist to date exactly Guinea and Fiji had got some Higham and his colleagues hit six known biological samples of their DNA from Denisovans. upon the idea of using tech- from Denisovans: three teeth This led to broad conclusions niques from proteomics – the and two bone fragments found about where the Denisovans study of proteins – which in in the Denisova cave in Sibe- had lived and when. recent years has begun to be ria, and part of a jaw found in All this came from a 2-cm applied to archaeology. They a cave on the Tibetan plateau. bone fragment determined used a technique called ZooMS The World Before Us: How Science is With so little material, conven- to be from the little finger of (Zooarchaeology by Mass Spec- Revealing a New Story of Our Human tional methods of identifying the right hand of a girl who trometry) to sift through bags Origins — Tom Higham species by their physical char- was thirteen-and-a-half years of bone fragments to find any Penguin Books acteristics cannot be used. It old when she died. From her that had human-like protein Pages 245+XXIV | Paperback is only because of recent leaps DNA it seems likely that she fingerprints. After labori- ` 799 in extracting ancient DNA that was dark-skinned, with brown ously running the process on these samples could be iden- hair and brown eyes. With the around 1,500 fragments, one of tified. When DNA from one sample being too old for radio- Higham’s master’s students, the earth around 50,000 years of the bone fragments did not carbon dating, Higham and his Samantha Brown, isolated a ago. And these groups didn’t match either modern humans colleagues developed a statisti- shard of human bone less than keep to themselves. They met or Neanderthals, researchers cal model that considered the 2 grams in weight. She named and interacted in ways we are concluded that it was from an age of related samples along it Denny. only beginning to learn about. unknown archaic human. with the rate of certain genetic What is behind this sudden changes. They estimated that HUMANISING DENNY clatter of skeletons from our FORENSIC ANTHROPOLOGY the girl had lived between 52,000 CT scans of the bone showed past? There are few better peo- As Higham explains, an ongo- and 76,000 years ago. that Denny was a young girl. 58

SHAASTRA 2021 May-Jun 14.indd 58 5/18/21 7:28 PM ©SJENNER13 /123RF.COM to examine our notions about what exactly a species is. Some of this new research allows for intriguing insights into ourselves. Higham points out, for instance, that being a ‘morning person’ has been linked with Neanderthal variants of certain genes. In Tibet- ans, it has been found that a Denisovan variant of the EPAS1 gene helps cope with living at high altitudes. A study comparing Han Chi- nese with Tibetans found that both populations were genetically close, with Den- isovans having made similar contributions to both their DNAs. Still, far more Tibetans than Han Chi- nese had the variant that helped with high altitude. The apparent mystery was resolved when it was established that both populations had received the variant from a common ancestral group, but the variant had In addition to genomics and proteomics, researchers are using a wide array proliferated only in those who settled at high altitude of techniques to flesh out details of humans from the past. because it gave them an advantage. Fascinating as Results of the genetic sequenc- to another. Ancient pollen can us. We overlapped with Nean- this is, it is not hard to imaging were so extraordinary that tell us about the vegetation in derthals in Europe for about ine that research on these lines it had to be done repeatedly an area during a particular ten thousand years, after which can have serious political im- for confirmation: Denny was period. Samples can be dat- the Neanderthals went extinct plications. Certainly in India, the daughter of a Denisovan ed with increasing accuracy for reasons that are not fully almost every announcement father and a Neanderthal moth- (thanks in part to Higham’s clear. But Neanderthals live on of results involving genetics er. Higham writes: “Denny was work), so we can tell not just in our DNA in a small but sig- or archaeology is subject to formerly anonymous, as so what happened but when. It is nificant way. There may also impassioned spin. A good use many human remains are in now possible to draw startling- have been cultural exchange of Higham’s book is to under- archaeology, and this tiny bone ly detailed portraits of indi- between the two populations. stand the methods by which is perhaps the last surviving viduals and populations who In the zone spanning Central these results are obtained and fragment of her. But gradually haven’t been around for tens of Asia to South-East Asia, we met prepare ourselves for the world we have been able to bring her thousands of years and to track the Denisovans, about whom that is before us right now. back into the light, to breathe their movements. we know less, but chances are Leaving aside contingen- life back into her and to recon- our interactions with them cies of the present, The World struct aspects of her existence. OUR JOURNEY went the same way as with Before Us leaves us with a Through this I think that we So, what is science saying Neanderthals. In South-East richer sense of our place on have begun somehow to honour about the world before us? In Asia, we may have encountered the planet. As Higham writes, her memory and give her story the broadest terms, we, modern Homo floresiensis (the so-called “The branchy tree of human to the world. In the process Den- humans, evolved in Africa be- Hobbits) and Homo luzonensis, evolution should instead be ny the ‘sample’, the ‘bone’, has tween 250,000 and 300,000 years both evolved from much older replaced with a wide braided become Denny the person.” ago. Though there had been migrations of humans from Af- river, whose tributaries often In addition to genomics and previous forays, we largely rica. There’s some chance that flow into and away from one proteomics, researchers are us- emerged from Africa between some of these older migrants, another… We are not simply ing a wide array of techniques 50,000 and 60,000 years ago, en- such as Homo erectus, might human, we are the sum of all to flesh out humans from the tered West Asia, Europe and just have hung around long of the branches of that braided past. Detailed reconstructions Asia, and, taking advantage of enough to get a glimpse of us, river that touched and parted of climate and sea levels are low sea levels and perhaps the and there may have been other on our way to today.” . 7 available to tell us what kinds occasional raft, moved through populations of archaic humans Srinath Perur writes on of migrations were feasible at South-East Asia all the way to we don’t know about yet. What science, travel and culture. He different times. Scientists can Australia. Along the way, we we do know is that we – Homo has previously written about now look at bones and teeth met Neanderthals in Europe, sapiens – are the only ones left. the origins of Indians, and and use isotope analysis to find who had been living there for This story will inevitably how ancient DNA helped find out what a person ate, at what a couple of hundred thousand be refined as more becomes a Georgian queen’s remains in age a child was weaned, when years, and who, it turns out, known. But already, all this Goa. someone moved from one area were not very different from inter-breeding is forcing us @sperur 59

SHAASTRA 2021 May-Jun 14.indd 59 5/18/21 7:28 PM FIRST PRINCIPLES The Standard Model of particle physics Tracing the evolution of the theoretical framework that laid the foundation for a broader understanding of matter. It seems ripe for a ‘rejig’. MISSMJ, CUSH

OMETIME IN the 5th century BCE, Greek philosopher Leucip- pus and his student Democritus Particles of matter Particles of interactions said that all matter was com- (fermions) (bosons) posed of atoms. There is some Scontroversy about who really first thought of the idea – Leucippus or Democritus – but the student, rather than the master, is now largely credited with first proposing that matter consisted of hard, indivisible particles called atoms. Democritus did not know what atoms were made of but posit- ed that matter became indivisible at some point. We then reach the smallest constitu- ent of matter, the atom. It was more philosophy than science. . Aristotle reigned supreme in Europe till the Renaissance, which meant that Dem- ocritus and his ideas were forgotten for 18 centuries. The first modern proponent of the atomic theory was John Dalton, a British chemist, who noticed that substances reacted with each other in definite, whole-number ratios. For example, hydrogen and oxygen combined in ratios of 2:1 to produce water. It was a good hint of the existence of atoms, but there was no direct evidence till Einstein formulated the theory of Brownian motion and Jean Perrin observed it in 1908. Brownian motion is the constant jiggling of particles in a fluid, caused by random motion of atoms. However, scientists knew that atoms were not indivisible – even before their The Standard Model explains a large number of natural existence was proved early in the 20th century. In 1897, British physicist J.J. Thom- phenomena, but it is not a complete theory. son observed a negatively charge particle during an experiment to discover the real nature of cathode rays. These rays are pro- raisins. The negative electrons and the at the source. The alpha particle, which duced when a high voltage is applied be- positive particles – the atom was neutral, we now know consists of two protons and tween the ends of a small tube from which and so there had to be positive particles to two neutrons, would bounce back only if most of the gas has been emptied. Thom- balance the charge – were distributed uni- it encountered a strong and concentrated son found that these rays consisted of a formly in the plum pudding model. This positive charge. Because most of the parti- stream of negatively charged particles idea didn’t last for very long. Ernest Ruth- cles went through the foil, the Rutherford that he called corpuscles, but they were erford, a New Zealand physicist at Cam- experiment showed that the atom was later renamed as electrons. It was obvious bridge University, found in 1911 that the largely empty space. Rutherford changed to scientists that the electrons came from positive charges were concentrated in the the plum pudding model into one based on within the atoms and hence the atom was middle of the atom and not spread around the solar system, with the positive charge not indivisible. the atom. concentrated in the middle and the elec- Rutherford had bombarded thin gold tron revolving around it. ‘PLUM PUDDING’ VS ‘SOLAR SYSTEM’ foils with positively charged alpha parti- In 1932, James Chadwick, another Brit- Thomson constructed a ‘plum pudding’ cles generated from radioactive materials. ish physicist, discovered the neutron. model of the atom in 1904, which looked Most of the particles went through the By the early 1930s, physicists thought rather like a breakfast muffin filled with foil easily, but some bounced right back they knew about all the particles required 60

SHAASTRA 2021 May-Jun 14.indd 60 5/18/21 7:28 PM © MAXIMILIEN BRICE / CERN The Higgs mechanism was used by Abdus Salam and Steven Weinberg in 1967 to develop a unified electroweak theory that combined the weak force and the electromagnetic force.

ish physicist Peter Higgs wrote in a paper in 1964 – it was initially rejected by journals – that a field present throughout the universe resists the motion of particles, and it is this resistance that is felt as the mass of the particle. The more a particle feels the field, the more massive the particle becomes. There are some particles – the photon – that do not feel the Higgs field and hence do not have mass. The Higgs field can produce a particle under certain condi- Prof Peter Higgs at the Large Hadron Collider at CERN. The discovery in 2012 of the Higgs tions. This particle, called the Higgs boson, boson particle is considered one of the greatest triumphs of physics. was discovered by scientists at the Large Hadron Collider in 2012. It was one of the to build the atom – and, by extension, all tineutrino. The neutrino was discovered greatest triumphs of physics. The Higgs matter in the universe. The neutrons and in 1956. mechanism was used by Abdus Salam and protons made the core of the atom, and the The list of elementary particles in- Steven Weinberg in 1967 to develop a uni- electrons moved around the core. Quan- creased in the 1960 and 1970s to beyond fied electroweak theory that combined the tum mechanics had forced scientists by 60. Nature was proving to be more com- weak force and the electromagnetic force. then to abandon the solar system analogy plex than scientists had imagined. In 1964, The electroweak force is an important in favour of the more fuzzy idea of orbit- American physicist Murray Gell-Mann part of the Standard Model. After Gell-Mann als, where the electron did not have precise theorised that the proton consisted of proposed the quark, physicists found them orbits around the nucleus of the atom. It smaller particles called quarks, the first mysterious. The protons and neutrons were was still a simple picture, consisting of a of which was discovered in 1968 at Stan- composed of three quarks, with different fla- few elementary particles. ford. Soon after the discovery of quarks, vours combining in different ways in each, Till 1932, the only other known particle physicists started building a model that but no single quark could be isolated. On the – apart from the electron, the neutron and explained all matter and their interac- other hand, quarks also moved freely within the proton – was the photon, the particle of tions. They classified the particles into two the proton at a very short distance. Three light. It wasn’t a particle like the electron main groups, the particles of matter and American scientists – David Gross, Frank or a proton, as it was not a building block particles of interactions, and formulated Wilzcek and David Politzer – deduced that of matter. Before the end of the 1920s, Brit- elaborate rules about what each particle the strong force was weak at very short dis- ish physicist Paul Dirac had predicted the can and cannot do. This model came to be tances inside the proton but became stron- existence of a positive electron; it was dis- known as the Standard Model of particle ger as they floated apart. At some distances, covered in 1932. In his Nobel lecture the physics. it would be so strong that the quarks can next year – it took only one year for the No- The particles of matter in the mod- never come off each other. So it seems that a bel Committee to award Dirac the prize – el were the electron, the muon, the tau, single quark can never be isolated. Dirac proposed an antiproton as well, with three kinds of neutrinos and six different the same mass but opposite charge as the quarks. The particles of interactions are UNANSWERED QUESTIONS proton. The antiproton took much longer exchanged during an interaction, creating The Standard Model explains a large num- to be discovered. Nature seemed to have a a force between the matter particles. The ber of natural phenomena but it is not a short-lived anti-particle for every particle. photon is exchanged for the electromag- complete theory. It does not reconcile two But, for no obvious reason, matter parti- netic force, the gluon for the strong nuclear major theories of physics: quantum me- cles dominated the universe. force, and the Z and W bosons for the weak chanics and Einstein’s theory of gener- nuclear force. These forces drove events in al relativity. It does not account for dark THE MYSTERIOUS MUON the universe. The strong nuclear force held matter, the mysterious substance that is In 1937, American physicists Carl Ander- the protons and neutrons together in the known to exist throughout the universe. It son and Seth Neddermeyer discovered nucleus. The electromagnetic force made does not explain why neutrinos have mass. the muon. It was an unusual particle atoms possible. The weak force was re- It does not explain why matter – and not that seemed to have no business to exist. sponsible for radioactive decay. The fourth antimatter – dominates in the universe. What purpose did the muon serve in the fundamental force, gravity, is supposed to Occasionally, physicists encounter anom- universe? It was like a heavy electron, be mediated by the graviton, but it has not alies of particle behaviour that cannot be with a similar negative charge, that was been directly detected yet. explained by the equations of the Standard so burdened by its weight that it disinte- Model. The muon experiment at Fermilab grated into an electron and another par- THE HIGGS BOSON (see story on Page 11) was one such anoma- ticle very quickly. This unknown particle There was one serious problem, however, ly. The Standard Model seems to be ripe for was thought to be the neutrino, but is now with the model. No one knew how the el- rejig. To be more precise, it is ready for a known to be its antimatter version, the an- ementary particles got their masses. Brit- significant extension. 7 61

SHAASTRA 2021 May-Jun 14.indd 61 5/18/21 7:28 PM COMPILER: KRISSKROSS FunTech ACROSS 1 2 3 4 5 7 Father’s weapon is one 3 Criminal cons Europe providing protection (8) with community software 6 7 9 Register kiss (not soft) in chin development (4,6)

8 (5-2) 4 Rule for data transmission 10 Stomp out an automated tool by randomly sorting various 9 10 for API development (7) package headers (4) 11 One redesigning her ancient 5 It indicates that the system is technique to create objects ready to accept your command (11) on time (6) 15 Electronic devices somewhat 6 Permission to use weapons, I useful at chess (7) hear (6) 11 12 18 Programming language 8 List of mind experiments (5)

13 supporting school - not current 12 LAN topology could be tree, (7) then mesh (8) 14 15 16 19 Record-breaking tribute to 13 Unfortunately Scottie is your favourite web site (4,4) missing a few bits (5) 14 Snake in skimpy thongs (6) 17 18 DOWN 16 Computer scientist going 1 IIT raged about internet around, losing heart (6) experts (8) 17 Online platform partially 19 2 Taxi returns with king to Indian rejected by a better (1-3) state to provide recovery from disaster (6)

QUIZ CLUB, IIT MADRAS

Where science intersects with popular culture

PopScience © ROMAN ZAIETS / 123RF in, coming on the shore of the nickname by which these her unsleeping mind.” That insects are known for their paragraph, from Ray Bradbury’s unique ability? Fahrenheit 451, written in 1953, is believed to have prophesied 5 In fire situations, people with a common and widely used hearing impairments cannot invention. Which is it? hear fire or smoke alarms go off. So, Japanese researchers 4 Gerridae are a family of insects came up with a novel idea: that have a unique ability: to they incorporated a very walk/skate on water! Their powerful, pungent substance two front legs and two hind in their fire/smoke alarms, so legs are far enough apart to that when they are triggered, spread their body weight over a the overwhelming smell wide surface area, and use the alerts residents to evacuate. water’s surface tension to stay They won an IgNobel Prize in 1 While performing life-saving 2 In January 2020, researchers on the water. Using their front 2011 for this invention. What cardiopulmonary resuscitation from Columbia University and legs to steer/row and their hind is this substance, which is (CPR), it is recommended Cold Spring Harbor Laboratory legs to propel themselves, they often consumed in Japan, in a that responders give chest revealed they had figured out move at over 1m/sec. What is different form? compressions at 100 pumps how a particular pheromone © LEO MALSAM / 123RF per minute. Keeping count helps mice attract and select isn’t always easy, so in CPR a mate. The pheromone was training sessions, practitioners named ‘Darcin’ – after a are advised to synchronise fictional character in a 19th- their chest compressions century romantic novel. Name with the beat of a song with the character. a similar beats-per-minute rhythm. Which is this hit 3 “And in her ears the little pop song from 1977, whose Seashells, the thimble radios name ties in with the spirit tamped tight, and an electronic of performing CPR (from the ocean of sound, of music and

patient’s perspective)? talk and music and talk coming

3. Earphones 4. Jesus bugs 5. Wasabi 5. bugs Jesus 4. Earphones 3. Prejudice and Pride Austen’s Jane from Darcy . Mr 2. Gees Bee by Alive Staying 1.

SHAASTRA 2021 May-Jun 14.indd 62 5/18/21 7:28 PM WORD GAMES CLUB, IIT MADRAS SPOONERISMS IT’S ALL G(R)EEK TO ME! A spoonerism is a pair of phrases that acquire two different meanings when their initial sounds/syllables are interchanged. For example, when a speaker says “He delivered a The given word or phrase or sentence holds blushing crow” when he intended to say “He two clues: taking away a Greek alphabet from a delivered a crushing blow”, that’s a spoonerism. synonym of the first half yields a synonym of the Named after Oxford don William Archibald second half. The numbers in brackets indicate Spooner, spoonerisms were initially considered the number of characters in each of the two errors in speech, or slips of the tongue, but they synonyms. can also signal a clever play on words. Example: Letter’s wager (8, 3) Example: String jumbo chess pieces together, to Solution: From the word Alphabet, which is an ANAGRAMS eight-letter word synonym for Letter, take away the peruse literature (4,5; 4,5) Scramble the given phrase to get the names of Solution: Bead rooks; read books Greek alphabet Alpha, and you’re left with Bet, a three-letter word synonym for Wager. renowned scientists. Alphabet – Alpha = Bet Example: Narwhales cried 1 Essential incentive for audio output device (3, Solution: Charles Darwin 4; 7) Now crack these 2 Ring electric beast of burden for building Now take a shot at these block (4, 1, 4; 8) 1 Held up banquet (8, 5) 3 Oscillating disturbance prevents beverage Aw, so ancient 2 Stacked up light sources (5, 3) 1 from falling (4, 4; 4, 4) Kin also late 3 Going to old monarch (8, 4) 2 4 Drag crustacean’s nucleon (3, 5; 6) Char many friend 4 Almost nothing for Musk (7, 4) 3 5 What setters do in proximity when full of Fresh router trend 5 Imitated Happy (8, 6) 4

explosive atomic energy (4, 4; 7) 5 He robs nil

Emulated – Mu = Elated = Mu – Emulated 5. 4. Tow Prawn; Proton 5. Clue Near; Nuclear Near; Clue 5. Proton Prawn; Tow 4.

3. Betaking – Beta = King 4. Epsilon – Psi = Elon = Psi – Epsilon 4. King = Beta – Betaking 3. Bohr Niels 5. Rutherford Ernest 4. Feynman 3. Sine Wave; Wine Save Wine Wave; Sine 3.

1. Detained – Eta = Dined 2. Piled – Pi = LED = Pi – Piled 2. Dined = Eta – Detained 1. Richard 3. Tesla Nikola 2. Newton Isaac 1. 1. Key Spur; Speaker 2. Call a Mule; Molecule Mule; a Call 2. Speaker Spur; Key 1.

SHAASTRA 2021 May-Jun 14.indd 63 5/18/21 7:28 PM TIME MACHINE A SYMBOL SETS OFF AN E-MAIL REVOLUTION In 1971, the @ symbol was ‘rediscovered’ and elevated to a defining symbol of the computer age. Today, it ‘delivers’ over 300 billion e-mails a day!

N THE realm of technology, the smallest incremental prog- Iress can occasionally cause the 1971 tectonic plates of history to shift dramatically, leading entire land- scapes to change. Just such an in- finitesimally small step – which has since translated into a giant leap for mankind – was taken 50 years ago, in early 1971, when the first “network e-mail” was sent out. DOWN THE AGES That came about when Ray Tom- Linguists reckon that the linson, a tech nerd from the Mas- history of the @ symbol Ray Tomlinson sent the first “network e-mail” to sachusetts Institute of Technolo- can be traced back to the gy (MIT), who was working for a 6th or 7th century CE: himself – from one Model 33 teletype machine to it was used in Latin to Massachusetts-based technology another, in the same room, connected through the fuse the preposition ad firm, used the @ symbol to send (meaning ‘at’ or ‘to’) into a mail between two machines. He ARPANET network. The US government agency a unique pen stroke. In was effectively sending a mail to that ran the project seized upon the possibilities it the 16th century, it was himself: the two machines were used by Venetian traders barely ten feet apart and were opened up. to refer to amphora, a “connected” only by the Advanced terracotta vessel, used as Research Projects Agency Net- explaining how to send messages a unit of measure. work (ARPANET), a US govern- over the network. ment-led project that proved the The choice of the @ symbol as precursor to today’s Internet of the connecting link was not moti- computers. The @ symbol, which vated by any compelling reason. we invoke unthinkingly while In media interviews at the time, sending e-mails today, served to Tomlinson noted that the @ sign THE MENAGERIE separate the user name from the (to be read as ‘at’) had been used in In Russia, the @ is known host name. It has since become accountancy protocols to specify a as sabachka (dog); the distinguishing characteristic unit price (for instance, 10 items @ Armenians refer to it as of all e-mail IDs that abide by the $1.95 each). “I used the sign to in- shnik (puppy); in Danish, user@host protocol. dicate that the user was ‘at’ some it is snabel-a (elephant’s There had been earlier instanc- other host rather than being lo- trunk); in German, it is es of mails being sent to numeric cal,” he had observed. Affenschwanz (monkey’s tail). mailboxes within a single ma- In 2010, the Museum of Modern chine, but there were no computer “brought about a complete revo- Art acquired the @ symbol into its SETTING THE networks as we know them today lution, fundamentally changing collection, noting that Tomlinson STANDARD until ARPANET came along in 1969 the way people communicate, in- had “rediscovered” an “underused The Internet Society as part of a defence project. cluding the way businesses, from jargon symbol” and “appropriated noted that in addition The social and economic sig- huge corporations to tiny mom- it, imbuing it with new meaning to contributing to nificance of that first “network and-pop shops, operate, and the and elevating it to a defining sym- establishing network e-mail” can be seen in the expo- way millions of people shop, bank, bol of the computer age.” That e-mail, Ray Tomlinson nential growth in its popularity. and keep in touch with friends and transformation has manifested played a leading role In 2020, an estimated 306.4 billion family, whether they are across itself in popular culture down the in developing the early e-mails were sent and received town or across oceans.” ages. The pop group Carpenters e-mail standards. He was each day, according to consumer The contents of that first e-mail crooned Please Mr Postman in 1975 a co-author of RFC-561, data firm Statista; that number is were “eminently forgettable,” re- and ghazal singer Pankaj Udhas the first standard for expected to rise to 319.6 billion a called Tomlinson, who was credit- induced diasporic nostalgia in 1986 Internet email message day in 2021, and further to 361.6 bil- ed with “inventing e-mail”. It was with Chitthi Aayi Hai; by the 1990s, formats, which defined lion a day by 2024. As the Internet likely a bit of gibberish, but once the message from Hollywood was many of the e-mail fields Society, which inducted Tomlinson he was satisfied that the program that You’ve Got Mail. That episto- (From, Subject and Date) into the Internet Hall of Fame in seemed to work, he sent out mes- latory revolution is still raging, 50 in use. 2012, noted, his e-mail program sages to the rest of his work-group years on. 7 64

SHAASTRA 2021 May-Jun 14.indd 64 5/18/21 7:28 PM CELEBRATING 60 YEARS OF CULTIVATING THE WORLD

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