How Indian biotech is driving innovation
Bolstered by government support, a wealth of investment and an eager graduate workforce, the country’s biotechnology industry is booming.
Anu Acharya was in her twenties when the human genome was first mapped in its entirety. In 2000, the young Indian entrepreneur was just breaking into the biotechnology arena with her first start-up — the genomics and bioinformatics company Ocimum Biosolutions in Hyderabad. She saw the Human Genome Project’s achievements as opening up a new world of possibilities in personalized medicine, informed by an individual’s genetic profile and predispositions — but at the time, the field of genomic medicine was dominated by Western science.
“I wanted to make sure that India had its own voice heard in that,” Acharya says. So, a decade later, she launched her second biotech start-up — molecular-diagnostics company Mapmygenome, also in Hyderabad — to bring the personalized-medicine revolution to India’s diverse population.
“Because, ultimately, when you’re making medicine precise, it has to be for specific individuals and populations rather than based on one population that has been studied.”
Acharya is among India’s rapidly growing ranks of biotechnology entrepreneurs and start-ups that are riding a wave of government enthusiasm, free-flowing venture capital and growing demand from an increasingly wealthy population that wants better treatment options. These factors are helping to drive India’s biotechnology industry beyond its historical focus on unbranded generic drugs and into the innovation limelight.
By the end of 2016, there were more than 1,000 biotechnology start-ups in India, and more than half of these had been established within the previous 5 years. Australia, by contrast, has 470 biotechnology companies and the United Kingdom 3,835. The biotechnology industry in India was valued at US$11 billion in 2016, and is forecast to grow to $100 billion by 2025.
More than half of the biotechnology start-ups are in the medical arena — diagnostics, drugs and medical devices — but 14% are in agricultural biotechnology, 3% in bioindustry, 1% in bioinformatics and 18% in biotechnology services.
India is already eyeing the prospect of its first biotechnology ‘unicorn’ — a start-up valued at more than $1 billion. The potential unicorn in question, Biocon in Bangalore, started in 1978 as an enzyme manufacturer but is now making a name for itself in the research and development of biological drugs for treating diabetes, cancer and autoimmune diseases. By March 2018, its revenue had topped $650 million.
India has long been a global player in the manufacture of generics (unbranded versions of existing pharmaceutical products), accounting for 20% of global exports of generics and earning just over $17 billion from that market in 2017. So what has prompted the nation to move beyond such a lucrative comfort zone and into the more risky game of biotechnology innovation?
In 1986, with the encouragement of then-prime minister Rajiv Gandhi, India became one of the first countries in the world to have a government unit dedicated solely to biotechnology. The Department of Biotechnology started with a relatively modest budget of between 40 million and 60 million rupees ($557,000–835,000), growing exponentially to 24.1 billion rupees in 2018. In addition to establishing 17 Centres of Excellence in Biotechnology at institutes and universities around the country, the department has supported the creation of 8 biotechnology parks, or incubators, in cities such as Lucknow, Bangalore, Hyderabad, Chennai and Kerala.
The aim of these parks is to provide facilities for scientists and small to medium-sized enterprises (SMEs), where they can develop and demonstrate their technologies and even build pilot plants. The hope is that this will speed up the commercialization process. The park staff also provide mentorship and guidance on issues such as intellectual property, business plans, proposals for clinical development and exit strategies.
This support is helping to address some of the logistical challenges that have hampered industry in the past, says Tej Singh, a biophysicist at the All India Institute of Medical Sciences in New Delhi and president of the Biotech Research Society, India.
“They created some sort of industrial regions in many areas, but there were issues like electricity, water [supply]; all these small things used to take time,” Singh says. “But the government has addressed these things nowadays; this current government particularly is very proactive.”
The Department of Biotechnology has also supported biotechnology research infrastructure, including a high-resolution mass spectrometry facility in Mumbai, flow-cytometry, imaging and microarray facilities in Delhi, and animal-house facilities in five other regions.
The jewel in the departmental crown, and the scheme that attracts the most attention, is the Biotechnology Industry Research Assistance Council (BIRAC). This is a not-for-profit, public-sector enterprise that was set up by the Department of Biotechnology in 2012 to “stimulate, foster and enhance the strategic research and innovation capabilities of the Indian biotech industry, particularly start-ups and SMEs”.
“The idea of forming BIRAC was to support the innovation ecosystem in India, and to nurture innovators from academia and industry to work independently or together,” says Shirshendu Mukherjee, mission director of the Program Management Unit at BIRAC. Mukherjee says India has always excelled at basic research but has faced challenges in translating that into commercial outcomes. BIRAC’s mission is therefore to “take innovation from the bench to the bedside, from the lab to the field, from the desk to the market”, he says.
In just six years of existence, BIRAC has supported 316 start-ups, which have generated $125 million through 122 products and technologies, including a cattle-feed supplement, a new process to manufacture human albumin and immunoglobulin, microfluidics-based diagnostics and a rapid test for malaria.
Its initiatives include ‘biotechnology ignition grants’ of up to 5 million rupees for start-ups and entrepreneurs to take a proof-of-concept through to the first major step on the path to commercialization. Another is a ‘glue grants’ scheme, which connects clinical-science departments with those for basic science in institutes and universities in the hope that this will encourage partnerships and collaborations.
BIRAC has also joined forces with the Bill & Melinda Gates Foundation in Seattle, Washington, on the Grand Challenges India initiative to tackle global health and development problems.
“I always call my Grand Challenges programme ‘in India, for India and beyond’,” says Mukherjee. “So we will do it in India, we will validate it in India, we will use it India, our citizens will use it, and then if it goes beyond India we are happy to do that.”
A similar motivation is driving at least some of the scientists and entrepreneurs such as Acharya, who get into the biotech space because they feel that Western biotechnology isn’t necessarily addressing the needs of the Indian population. One example is Vivek Wadhwa, a technology entrepreneur at Harvard Law School in Cambridge, Massachusetts, and at Carnegie Mellon University’s College of Engineering at Silicon Valley, California, who has invested in Indian medical-diagnostics company HealthCube in New Delhi.
“I did a big study on the pharmaceutical industry in India, and I concluded that Western companies were not addressing Indian disease because it wasn’t profitable enough for them,” Wadhwa says.
But as the cost of technologies such as genome sequencing and medical sensors comes down, Wadhwa says, it has now become viable for Indian biotechnologists to harness these advances for the Indian market.
And what a market India is for these innovations. The country’s population is 1.36 billion and rising, and health care is one of India’s fastest-growing sectors, driven by higher incomes and an increasing prevalence of lifestyle diseases, such as heart disease and stroke. By 2022, the health-care market in India is expected to be worth $372 billion.
“People are finally realizing that the consumer, or the patient, actually has control over their own health,” says Acharya. The rising middle class wants better health and medical choices, and she says that’s one of the main drivers for investment in biotechnology research and development.
For example, Biocon has developed the first recombinant insulin to be produced in India, and an antibody-based treatment for head and neck cancer. In 2017, Indian vaccine manufacturer Bharat Biotech in Hyderabad began the first clinical trials of its vaccine against the mosquito-borne virus chikungunya, which re-emerged in India in 2006 after 32 years and infected more than 1.4 million people.
Another major driver of the biotechnology boom in India is the accessibility of funding, from both government and private industry. In one 2016 report on biotechnology, India ranked only 49th out of 54 countries. But it scored particularly highly on the availability of venture capital compared to countries such as the United Kingdom, Australia and Canada.
Acharya says that some of the investors who have made their fortunes in manufacturing generic pharmaceuticals are now investing in biotechnology. She says much of the capital investment in early-stage biotechnology is coming from India, whereas investment in medical devices is flowing from Japan, China and the United States. But late-stage investment is still an issue.
“A lot of early-stage start-ups are getting funded but I think the challenge is still the late stage,” she says. “It’s not just the first two to three years; it’s more how do you take it from start-up to scale-up? I think that’s the challenge in terms of getting to where we need to get in terms of biotechnology.”
One thing India has plenty of is people. Recognizing that human capital can be a key resource for a nation not as well endowed financially as Western countries such as the United States or United Kingdom, the Department of Biotechnology implemented or supported various training initiatives. These include the Biotech Industrial Training Programme, set up in 1993 for recent graduates, and 12 Biotech Finishing Schools in Karnataka state to train Indian graduates and researchers in biotechnology.
That programme “created a very large number of institutions or departments of biotechnology in institutions and also departments of bioinformatics”, says Singh. For example, in September, the state of Gujarat proposed India’s first university focused entirely on biotechnology.
“A decade or so ago, India didn’t have the engineers or scientists it does today — it’s been graduating them in droves,” says Wadhwa. “It has millions of technologists who now just need to be connected to the medical practice and they can be solving great problems.”
Singh notes that these graduates aren’t waiting for a job to walk up and tap them on the shoulder; they’re taking matters into their own hands. “Graduate students who come out in large numbers from Indian institutes of technology and institutes of management are not looking for jobs so much; they create small start-ups and then they grow very fast,” Singh says.
Working in biotechnology in India does present its own unique set of challenges, says Acharya. “Some operational things that you never have to think about in the United States you have to plan more in India, because a lot of times we are still importing the reagents and things like that.”
Although the government of India is enthusiastic about supporting the biotechnology industry, Acharya says the regulatory process for getting products approved could be more streamlined.
In agricultural biotechnology, the government’s Genetic Engineering Appraisal Committee has been working to make it easier for companies to get approval for genetically modified crop field trials from state governments.
The drug approvals process in India has hit some rough patches in recent years, and the authors of a 2017 World Health Organization report suggested that innovation there could be outpacing regulation. Even the government’s own National Biotechnology Development Strategy for 2015–20 acknowledges that timelines and regulatory steps for biotechnology drug approvals are not user-friendly. It has proposed reforms, including the establishment of regulatory departments that are fluent in good practice in the clinical, manufacturing and laboratory arenas.
There are also concerns about the environmental impact of India’s pharmaceutical industry. An investigation in 2016 found “unprecedented” levels of pharmaceutical pollution in the water system of Hyderabad (C. Lübbert et al. Infection 45, 479–491; 2017), which is home to a significant proportion of biotech start-ups and generics manufacturers. However, as the US Food and Drug Administration reportedly steps up inspections of overseas pharmaceutical suppliers, environmental standards could be forced to improve.
Despite the challenges, there is palpable excitement about what lies ahead. “Right now, we are seeing the beginnings of a revolution in biotechnology in India,” Wadhwa says.
Acharya is still fired with the same enthusiasm that propelled her into biotechnology nearly two decades ago. “Any innovation in this space can actually impact lives,” she says. “That’s why I continue to be in it.”
This article is part of the Nature Spotlight on Indian biotechnology, an editorially independent supplement. Advertisers have no influence over the content.
Q&A: Living and working in India
In this article, Puthusserickal A. Hassan discusses balancing research and home life in India. What do you do? I am a full-time research scientist working in the field of self-assembled materials. Currently, our focus is to understand the role of antifreeze protein mimics in sustaining self-assembly at sub-zero temperatures. My research objective is to understand how small molecules undergo association in various solvents or experimental conditions, leading to an entire gamut of structures with nanometre-scale features. Looking at the structure-property correlations of such colloidal assemblies gives an insight into the role of intermolecular interactions in governing the microstructure. Many natural systems rely on such intermolecular associations to develop macroscopic objects to carry out specific functions or even to modulate their existence in extreme conditions. Puthusserickal A. Hassan Head, Nanotherapeutics and Biosensors Section, Bhabha Atomic Research Centre Do you enjoy it? Why? In my opinion, research is something you explore using your brain and sophisticated tools to understand how various processes happen in nature. Each experiment is a learning experience and gives new information which is hitherto unknown. By seeing new results, I feel like a child who gets to play with a new toy every day. What was your earliest career ambition? My ambition was to become a teacher with resources for research. During my graduate days, I wondered if I could see, one day, organic molecules the way that they are depicted in textbooks. Later, I realised that no one saw the molecules, but that the structures were deduced from a combination of different spectroscopic tools. What are some of the challenges in your job? The challenge today is that most of the scientific problems we try to address require interdisciplinary expertise. You need to expand your knowledge base by cutting across disciplines to understand how things work in nature. How do you deal with those challenges? Collaboration with experts is the best way to meet this challenge. It is not only the advanced instruments you use that are important, but also the proper utilisation and interpretation of data, which needs specialised learning across disciplines. Through discussions and collaborations with physicists and biologists, many challenges can be tackled. How does being based in India affect the way you work?< Research becomes successful once it is translated into products on the market. Despite having a good number of skilled workers, Indian industry lacks disruptive innovation. I feel that this is primarily because Indian industries do not invest enough in completely new products or processes, fearing commercial failure. For example, most pharma companies focus on the supply of generic drugs and very few attempts are being made at drug development. By incentivising industrial R&D in high-risk areas and supporting industry-academia joint projects, the transition from lab to land can be realised in many niche areas. What advice would you have for others trying to work in a similar sort of environment? It is a wonderful experience to explore new things in science. My advice is that one should first become a master in a specific area of interest. This mastery can be gained by nurturing a new idea that is just reported. This will provide the opportunity to gain knowledge about the tools and techniques needed for the specific problem. The next step is to think beyond what is reported. Speculate on an idea and see if you can prove that by using the tools you have acquired. When you prove an idea that was previously unknown, the excitement is unimaginable. What do you love about living and working in India? I love the culture of the place where I grew up. Living in India helps me to connect with my close relatives. Balancing my professional life with family, parents and relatives has been a top priority for me and being in India has made this possible. What's your top career tip to younger colleagues? First, assess your ability to explore new things in science. There may be several hurdles and failures along the way to cracking one problem. But the excitement you get once you resolve the issue is phenomenal. If you love exploring things that you have not come across before, go for research. What else would you say to others trying to build a scientific career in India? India is a hub of opportunity and it needs scientific solutions to help tackle many of its local problems – water purification, affordable healthcare and low carbon emission technologies, to name a few. This is both a challenge and an opportunity for young researchers. By addressing these challenges, you can help create an impact in society. If you have a career story that you'd like to share, then please complete this form, or send your outline by email.
India debates a nationwide tenure system
Academic staff disagree on the merits, and the downsides, of scrapping a common year-long probation scheme. Academic researchers and administrators in India are debating the benefits of adopting a tenure-track system similar to that of the United States in Indian research institutes and universities. A few, including the Indian Institute of Science in Bengaluru, are already using the system, whereas others, such as the Indian Institutes of Technology, have a probationary-period process. Under that scheme, the performance of new faculty members is assessed after one year by a review committee, often comprised of department heads and institutional administrators. Some scientists are calling for the nationwide adoption of a five-year tenure-track review structure. After around five years, research faculty members are reviewed on the basis of their publications and funding received. Teaching ability and service to the institution usually have a supporting role. If the candidate is granted tenure, they receive a permanent appointment. If they are not, the appointment is terminated. Under the probationary system in India, research faculty members who receive a positive assessment at the end of their first year are given permanent positions as assistant professors. After another five years, they can apply to become associate professors — a position with higher rank and pay. If they are unsuccessful, however, their appointments are not terminated. Faculty members can stay at their institutions as assistant professors until they retire. Those who endorse the tenure-track system say that the probationary system allows low-performing researchers to remain in their posts. “How do we ensure that quick appointments to a very well paid, highly privileged and permanent position does not encourage complacency?” asks ecologist Vishwesha Guttal, who was awarded tenure in 2016 at the Indian Institute of Science, five years after he was hired. The issue of tenure-track versus one-year probation has sparked discussion and debate among academic scientists in India, partly in response to an interview published in June in the newspaper Hindustan Times with Jayant Udgaonkar, director of the Indian Institute of Science Education and Research in Pune. In the interview, he advocated adopting the tenure-track system nationally. His comments followed the release of a draft policy in May by the Ministry of Human Resource Development, which oversees higher education in India, recommending a gradual national adoption of the tenure-track system. The ministry could not be reached for comment. Udgaonkar, a biochemist, says that it is difficult to properly assess a researcher’s progress in a single year. He thinks that the tenure-track system provides scientific accountability and allows a candidate who has been given strong support and regular feedback to receive a comprehensive assessment at the end of five or sometimes seven years. But many do not agree. Theoretical physicist Arvind, director at the Indian Institute of Science Education and Research campus in Mohali, says that a five-year tenure track will increase job insecurity and put pressure on new faculty members to pursue only short-term research goals during that period. “Academia requires stability,” he says, adding that there is a paucity of fallback options for candidates who don’t make the cut. India has few second- or third-tier research institutions where a scientist whose bid for tenure is rejected elsewhere can seek another appointment, and few commensurate industry positions. Institutional support, easy access to equipment and resources, and timely disbursal of government grant funds have long been sore points in Indian academia; they have also been a talking point in discussions about adopting a tenure system. Gagandeep Kang, an academic gastroenterologist and executive director of the Translational Health Science and Technology Institute in Faridabad, says that institutions and government need to improve access to funding and resources to level the playing field for researchers who are up for tenure and allow for a more-rigorous review process. Ramaswamy Subramanian, a structural biologist and director of the Bindley Bioscience Center at Purdue University in West Lafayette, Indiana, says that if tenure is adopted, the process will need to be uniformly objective and fair. Subramanian, who has held tenured positions in Sweden and the United States, points out that tenure-review committee members in India, usually senior scientists and administrators, are likely to lack personal experience of the process. A nationwide system is unlikely to be adopted soon, predicts Arvind. “Each institution is autonomous,” he says. “There may, at best, be suggestions that the governing boards of individual institutions can then consider.” If you have a career story that you'd like to share, then please complete this form, or send your outline by email.
Focusing on the Negative is Good When it Comes to Batteries
New concept based on fluoride ions may increase battery lifespansNews Writer: Whitney Clavin An illustration of the electrolyte solution used in the new study, on the atomic scale. The fluoride ion (pink) is surrounded by a liquid of BTFE molecules.Credit: Brett Savoie/Purdue University Imagine not having to charge your phone or laptop for weeks. That is the dream of researchers looking into alternative batteries that go beyond the current lithium-ion versions popular today. Now, in a new study appearing in the journal Science, chemists at several institutions, including Caltech and the Jet Propulsion Laboratory, which is managed by Caltech for NASA, as well as the Honda Research Institute and Lawrence Berkeley National Laboratory, have hit on a new way of making rechargeable batteries based on fluoride, the negatively charged form, or anion, of the element fluorine. "Fluoride batteries can have a higher energy density, which means that they may last longer—up to eight times longer than batteries in use today," says study co-author Robert Grubbs, Caltech's Victor and Elizabeth Atkins Professor of Chemistry and a winner of the 2005 Nobel Prize in Chemistry. "But fluoride can be challenging to work with, in particular because it's so corrosive and reactive." In the 1970s, researchers attempted to create rechargeable fluoride batteries using solid components, but solid-state batteries work only at high temperatures, making them impractical for everyday use. In the new study, the authors report at last figuring out how to make the fluoride batteries work using liquid components—and liquid batteries easily work at room temperature. "We are still in the early stages of development, but this is the first rechargeable fluoride battery that works at room temperature," says Simon Jones, a chemist at JPL and corresponding author of the new study. Batteries drive electrical currents by shuttling charged atoms—or ions—between a positive and negative electrode. This shuttling process proceeds more easily at room temperature when liquids are involved. In the case of lithium-ion batteries, lithium is shuttled between the electrodes with the help of a liquid solution, or electrolyte. "Recharging a battery is like pushing a ball up a hill and then letting it roll back again, over and over," says co-author Thomas Miller, professor of chemistry at Caltech. "You go back and forth between storing the energy and using it." While lithium ions are positive (called cations), the fluoride ions used in the new study bear a negative charge (and are called anions). There are both challenges and advantages to working with anions in batteries. "For a battery that lasts longer, you need to move a greater number of charges. Moving multiply charged metal cations is difficult, but a similar result can be achieved by moving several singly charged anions, which travel with comparative ease," says Jones, who does research at JPL on power sources needed for spacecraft. "The challenges with this scheme are making the system work at useable voltages. In this new study, we demonstrate that anions are indeed worthy of attention in battery science since we show that fluoride can work at high enough voltages." The key to making the fluoride batteries work in a liquid rather than a solid state turned out to be an electrolyte liquid called bis(2,2,2-trifluoroethyl)ether, or BTFE. This solvent is what helps keep the fluoride ion stable so that it can shuttle electrons back and forth in the battery. Jones says his intern at the time, Victoria Davis, who now studies at the University of North Carolina, Chapel Hill, was the first to think of trying BTFE. While Jones did not have much hope it would succeed, the team decided to try it anyway and were surprised it worked so well. At that point, Jones turned to Miller for help in understanding why the solution worked. Miller and his group ran computer simulations of the reaction and figured out which aspects of BTFE were stabilizing the fluoride. From there, the team was able to tweak the BTFE solution, modifying it with additives to improve its performance and stability. "We're unlocking a new way of making longer-lasting batteries," says Jones. "Fluoride is making a comeback in batteries." The Science study, titled, "Room Temperature Cycling of Metal Fluoride Electrodes: Liquid Electrolytes for High Energy Fluoride–Ion Cells," was funded by the Resnick Sustainability Institute and the Molecular Materials Research Center, both at Caltech, the National Science Foundation, the Department of Energy, and the Honda Research Institute. Other authors at Caltech during the study include Christopher Bates, Brett Savoie, Nebojša Momčilović, William Wolf, Michael Webb, Isabelle Darolles, and Nanditha Nair.