Multidisciplinary Research: Pros and Cons
By bringing together experts from different disciplines we can find the solutions for today’s global challenges. Having spent a year in a multidisciplinary research group, Mit Bhavsar shares his thoughts on the advantages and disadvantages of multidisciplinary research in science.
The increasing popularity of mixed scientific disciplines like mechatronics, bioinformatics, biomedical engineering and biophysical chemistry is evidence of the importance of multidisciplinary. And, based on the number of multidisciplinary conferences taking place around the world, it seems that many policymakers agree that bringing scientists from a variety of different backgrounds together is a crucial part of fixing the world’s problems.
Going multidisciplinary does not mean leaving behind your own skills — it means heading in new scientific directions using your own specialties. I completed a neurophysiology PhD in a monodisciplinary research group. Now, I’m working as a postdoc in a multidisciplinary research group in the field of regenerative medicine. Here are my perceived advantages and challenges.
One problem I’ve found with a monodisciplinary research group is a lack of creativity when it comes to working out what kind of work can be done. A multidisciplinary group can combine the expertise of your field with other fields and create a varied team. Such combination can lead to creative and high impact research. For example, my lab is working on tissue regeneration and repair through electrical stimuli. For such kind of research, one often needs expertise in the field of medicine and electrical engineering.
For me, the most attractive part of multidisciplinary research is that you can work on projects that involve more than one discipline of science. This meant honing my existing skills and learning a whole lot more from scientists I’d never previously had a chance to interact with. As well as that, because I’m the only expert in my field in my group, I can work independently to address problems when they come up.
Multidisciplinary research also leads to unusual scientific inventions. A lot of great science has come from the robust interactions of researchers from different fields. A good example of this is the discovery of “Magnetic resonance imaging” by Paul Lauterbur (a chemist) and Peter Mansfield (a physicist) — for this they were awarded the 2003 Nobel prize in Physiology or Medicine. An independent researcher designing and conducting their own separate experiments would never have had these opportunities.
One of the common challenges of working in a multidisciplinary research group is a lack of a “common language.” It’s hard to find a way to start working on a problem when everyone has been trained to approach it from different directions. For me, this makes it difficult to discuss ideas with team members and get the right feedback. This problem feeds into feeling of loneliness — I’m surrounded by lab mates but I’m the only one working on this particular problem in this particular direction in my lab. Another issue: there is no meaningful criticism and evaluation of your work. Your ideas and suggestions are either accepted without any questions or they will be rejected without constructive criticism.
If you can deal with these challenges, it can be very rewarding to do multidisciplinary science. To facilitate multidisciplinary research, universities and research institutes should encourage interaction between different disciplines where scientists can meet, share ideas and discuss problems.
Mit Bhavsar is a researcher living and working at Frankfurt Initiative for Regenerative Medicine (FIRM) Frankfurt, Germany. You can contact him on: firstname.lastname@example.org
A general reinforcement learning algorithm that masters chess, shogi, and Go through self-play
The game of chess is the longest-studied domain in the history of artificial intelligence. The strongest programs are based on a combination of sophisticated search techniques, domain-specific adaptations, and handcrafted evaluation functions that have been refined by human experts over several decades. By contrast, the AlphaGo Zero program recently achieved superhuman performance in the game of Go by reinforcement learning from self-play. In this paper, we generalize this approach into a single AlphaZero algorithm that can achieve superhuman performance in many challenging games. Starting from random play and given no domain knowledge except the game rules, AlphaZero convincingly defeated a world champion program in the games of chess and shogi (Japanese chess), as well as Go.
How Indian scientists have been scrambling to contain antimicrobial resistance for years
In 2017, the World Health Organization (WHO) came up with a new classification system for antibiotics on its essential medicines list: Access, Watch, and Reserve. Antibiotics on the Access list were narrow spectrum antibiotics — only effective against a small range of organisms — that would be recommended as first and second treatment options for common clinical infections. Those on the Watch list were broader spectrum, able to tackle a wider range of pathogens and therefore considered more important for human medicine. The Reserve list describes antibiotics of last-resort; only for use when all other antibiotics had failed. As SARS-CoV-2 wreaks havoc around the world, antibiotics have fallen off the agenda; they are completely ineffective against a viral infection. But antibiotics do work against the disease-causing bacteria that are responsible for millions of deaths worldwide each year. Antibiotic resistance was a critical health issue long before COVID-19 exploded into hospitals and headlines, and it will continue to be one long after the pandemic has been brought under control. Antibiotics on the Access list are the ones that should be the most widely available and the most widely used, and the WHO says by 2023, 60% of all antibiotics consumed should come from the Access group. Unfortunately in India, that trend is going in the opposite direction, says Jyotsna Singh, program officer at humanitarian organisation Medicins Sans Frontiers’ Access campaign in Delhi. One 2017 analysis found that while sales of key Access antibiotics had risen 20% since 2007-2008, sales of Watch group antibiotics had risen by 73% and sales of Reserve antibiotics increased by 174%. “What we are seeing is that in the Access category there are medicines which are in shortage, which is becoming a huge problem,” Singh says. It means that instead of treating infections in a targeted fashion, with antibiotics specifically tailored to individual pathogens, doctors are using broader spectrum antibiotics from the Watch and Reserve categories. Not only are these antibiotics supposed to be used only for more difficult infections, but they are associated with a higher likelihood of resistance developing. “You have to save Watch and Reserve for certain infections which cannot be treated otherwise,” she says, “or in the long term patients’ health will be put at risk.” This has already cost lives. Each year, more than 58,000 newborns in India are estimated to die from bacterial sepsis that is resistant to first-line antibiotics. Individuals in India infected with bacteria resistant to more than one antibiotic are two to three times more likely to die than those with non-resistant infections. Another study has found that 40 per cent of pregnant women and 60 per cent of schoolchildren are carrying strains of E. coli bacteria resistant to at least one antibiotic. In 2019, India scored highest of 41 countries on the Drug Resistance Index — a measure combining both antibiotic use and resistance levels, and by 2050, antimicrobial resistance has been forecast to claim an additional two million lives per year in India. But Satya Sivaraman, who develops communications strategies on antibiotic resistance with ReAct Asia Pacific — one arm of the global ReAct network created in 2005 to focus on antibiotic resistance — says many healthcare professionals face a bigger issue. “If you talk to doctors on the ground about antimicrobial resistance, they’ll say ‘yes it’s a problem in some cases, but the bigger problem is that we don’t have antibiotics at all,’” says Sivaraman. In a country with such a high incidence of infectious disease, the lack of any treatment is killing more people than treatment resistance. It also means India is a huge reservoir of infectious pathogens: a “factory of disease production,” he adds. At the same time, antibiotics are being overused and misused to such an extent that even India’s massive generic drug manufacturing industry can’t keep up with demand. New antibiotics Singh says generic drug manufacturers — many of which produce copies of brand-name medications in India’s thriving pharmaceutical manufacturing sector — blame the shortage on the low price set for antibiotics by India’s price control mechanism, which limits what pharmaceutical companies can charge the government and consumers for essential medicines and makes them a far less attractive business. Some state governments in India are taking matters into their own hands to ensure a supply of antibiotics. In 1974, for example, the state government of Kerala established its own, government-run pharmaceutical manufacturing operation — Kerala State Drugs and Pharmaceuticals — which supplies essential and life-saving medicines, including antibiotics, to government hospitals. The other problem is that, around the world as well as in India, pharmaceutical companies are pulling out of research and development of new antibiotics, leaving it to governments to pick up the slack. Sidarth Chophra, microbiologist and professor at the Central Drug Research Institute (CSIR) in Lucknow, India, is hunting for new molecules specifically targeted at drug-resistant bacteria. One focus is the so-called ESKAPE pathogens which are responsible for the majority of hospital-acquired infections and which all show resistance to multiple existing antibiotics. CSIR is directly funded by the Indian government. The speed with which bacteria evolve resistance to new antimicrobials presents a huge challenge, says Chopra. “I tell my students all the time, this is like playing chess with a grand master,” he says. Chopra and colleagues are trying every trick in the book to gain the upper hand. First, they’re looking at existing drugs to see whether any might also show antimicrobial activity, because that can help speed up the drug development and testing process. One molecule showing antibiotic properties is disulfiram, which is normally used to treat chronic alcoholism. They’re also looking at molecules that might otherwise not be considered potential candidates because they don’t meet the so-called Lipinski’s rule of five for predicting compounds that are likely to succeed as drug candidates. “We are more than happy to look at unconventional molecules which a normal medicinal chemist would not touch with a barge pole,” Chopra says. Funding healthcare Even if vital antibiotics become more widely available in India, there is still the problem of how, in a country with an overwhelmingly private healthcare system, many citizens could afford to access the doctors who prescribe them. A report published in April this year by the Center For Disease Dynamics, Economics & Policy, a public health research organisation based in Washington DC and New Delhi, found that 65% of health expenditure in India comes from the pockets of individual patients, compared to 13% in Germany. The cost of health care is estimated to drive 57 million Indian residents into poverty each year. Philip Mathew, a public health consultant with ReAct, says that universal health coverage might help enable many poorer patients to access essential medicines such as antibiotics. “A universal health care system in developing countries can solve many, many issues associated with access to essential antibiotics,” he says. The Indian government is moving in that direction. In 2018, it announced the creation of the ‘Ayushman Bharat — National Health Protection Mission’ to provide health coverage worth up to 500,000 rupees (US$7,000) per family for 100 million poor and vulnerable families. The plan also includes ‘health and wellness centres’, which are intended to provide primary care, free diagnostic services and essential drugs. But there are questions about how the government of India will pay for the scheme, given its spending on public health is one of the lowest among low-middle income countries. Another challenge is ensuring that clinicians in that healthcare system prescribe antibiotics appropriately. Because of their seemingly miraculous curative powers, antibiotics have become a victim of their own success. Patients — not just in India but around the world — have come to view antibiotics as a magic bullet for all ailments, and expect them from their doctor. “They are paying some fee to the private doctor for the consultation, and they want to know that they’ve actually taken some strong medicine back with them, so this whole cycle, the patient-doctor cycle, is completely skewed,” Sivaraman says. This situation is further exacerbated by climate change, which is changing patterns of infectious disease outbreaks, and contributing to the emergence of new diseases for which there are no or only recently developed vaccines, such as dengue and chikungunya. The latter re-emerged in India in 2005 after a twenty-year hiatus and since then, over one million cases of the mosquito-borne viral infection have been reported. A vaccine is now available, but has limited efficacy. “These viral fevers get confused with bacterial infections and then people tend to use antibiotics, so that contributes to the problem,” says Jyoti Joshi, head of South Asia at the Center for Disease Dynamics, Economics & Policy in New Delhi. Changing the minds of doctors is one thing; changing the expectations of patients is another, says Ramanan Laxminarayan, director of the Center for Disease Dynamics, Economics & Policy in Washington DC. “Here you’re saying ‘don’t take an antibiotic, not because it will necessarily harm you but because you’re ruining the chances for someone else to be treated with that antibiotic. Human beings tend to work in selfish ways and in this instance it doesn’t work out so well for us.” Cost of resistance Every year in India, 1 million children die in the first four weeks of life. 190,000 of these deaths are attributable to neonatal sepsis, and just over 30% of those sepsis deaths are attributable to antibiotic resistance. But the true scale of the antibiotic resistance is concealed by a lack of data because when someone dies in hospital from infection, it’s rarely recorded as a death from antibiotic resistance. “It’s not something that the common man observes to say, ‘oh my God: people are dying of drug resistance’,” Laxminarayan says. It is clear, at least, that antibiotic resistance rates continue to increase. Since 2008, the proportion of pathogenic bacteria found to be resistant to important antibiotics has risen significantly; in some cases, tripled or even quadrupled.. In 2017, the Indin government released its National Action Plan on Antimicrobial Resistance. This identified six strategic priorities including improved awareness, better surveillance, reducing infection rates, and improved antibiotic stewardship. The priorities were aligned with global action plans on antibiotic resistance, but Joshi says this approach is not a magic bullet for all developing countries. “The models that have worked in the ‘developed’ world cannot be copied back and implanted here … so you can't copy and paste,” she says. While India now has an action plan, she says it’s going to take some time for that cookie-cut plan to adapt to the Indian way of doing things. “We need to really dirty our hands and get models that work for us in our settings with all the resource limitation and competing priorities, and try them out to control the scourge of antimicrobial resistance,” she says. While there are likely to be successes and failures, she believes the country will learn from those experiences, “and then come out and say, ‘yes, this is what can be done, and this is how it should be done.’” Antibiotics in agriculture Studies show that India’s booming poultry industry is a potential danger to health. By Bianca Nogrady, a freelance science writer in Sydney, Australia While antibiotic use in agriculture has caused headaches in many western countries, India’s primarily vegetarian diet has meant the problem of agricultural antibiotic use is much less severe. But, thanks in part to a booming poultry industry, it’s becoming a bigger issue. Poultry samples have found resistance rates to streptomycin as high as 75%. Resistance rates to other antibiotics including ampicillin and rifampicin were over 40%. “You have these huge poultry farms where there’s a huge amount of overcrowding, and antibiotics are used to cover up your hygiene and biosecurity practices,” says Robin Paul, Quality Manager in the State Laboratory of Kerala’s State Veterinary Department in Kochi. A 2019 study identified India and China as the largest low-middle income global hotspots of antimicrobial resistance in animals, and singled out the antibiotic colistin — an antibiotic that the WHO recommends be reserved to treat multi-drug-resistant human infections — as a particular source of resistance and public health concern. In July 2019, India followed China and banned the sale and use of colistin in the agricultural industry, because of the risk to human health. But Paul says more needs to be done to help farmers better manage their farms without resorting to antibiotics. “The crux of animal health is to manage the health of animals so that they don’t need to go on antibiotics,” he says. 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India’s Commitment to Science Begins to Pay Off
Illustration by Michelle Thompson; Photos: Getty, Shutterstock A push to reverse its brain drain is providing the expertise to tackle its domestic problems. When Anil Koul told his friends that he would be moving to India to start working at a government research and development organization, most of the reactions were of disbelief, “even sympathy”, he says. “Some thought it was a crazy idea — moving from the world’s largest health-care giant to a governmental, bureaucratic set-up.” Koul took charge of the Institute of Microbial Technology (IMTECH), in the northern city of Chandigarh, in 2016, relocating from Johnson & Johnson in Belgium, where he was senior director and head of the respiratory diseases group. The move to IMTECH — a branch of India’s government-run Council of Scientific and Industrial Research — was atypical. Few scientists return to India after holding top positions abroad, and fewer still move into the less-lucrative public sector. The scientific landscape that Koul has returned to is vastly different from the one he left in 1998. India is now actively participating in and, in some cases, leading advances in pharmaceuticals, agriculture and energy. The country’s efforts in space exploration are a point of particular national pride. India is preparing for its second Moon mission in 2018 after a successful maiden Mars mission in 2014, and is spreading its wings in international astronomy collaborations. The country will host the third laboratory of the Laser Interferometer Gravitational-wave Observatory (LIGO) project in Hingoli, while the National Centre for Radio Astrophysics in Pune is working on the design of the ‘Telescope Manager’ — the central command system of the Square Kilometer Array. These could be signs that India is enjoying ‘brain gain’ — Indian researchers are returning to their country of birth with newly minted research skills gained while abroad. This is a far cry from the state of the country’s scientific sector 40 years ago, when entire cohorts of graduates from India’s research institutes left for US institutions in search of better economic and educational opportunities. “We are now in an era of globalization and international cooperation,” says immunologist Indira Nath, a member of the Indian National Science Academy. “Scientists going abroad is no longer a big issue.” To-do list But India still faces significant challenges. It is home to one-quarter of the world’s tuberculosis (TB) cases, and continues to be ravaged by mosquito-borne infections including malaria and dengue fever. Around 700 million Indians (56% of the country’s population) have no sanitation, 240 million have no access to electricity and 97 million lack clean drinking water. Natural disasters such as droughts, floods and storms — already common across Southeast Asia — are set to increase in frequency and ferocity as the world’s climate changes. It falls on publicly funded research to take the lead in finding solutions. Since India gained independence from British rule 70 years ago, every prime minister has emphasized the role of science in the country’s development. The current incumbent, Narendra Modi, told a meeting of leading Indian science officials in July that science, technology and innovation are the keys to the progress and prosperity of India and that the government aims to apply science to solve the country’s problems. As various policy initiatives make clear, India is betting on science to address its pressing challenges in energy, environmental protection, food, water, sanitation, health care and unemployment. To achieve this, the government is hoping to find more scientists like Koul, who sees his role as an “opportunity to address bigger social as well as scientific challenges”. This is a tall order, and there’s an elephant in the room. Government funding for Indian research and development has stagnated at around 0.85% of gross domestic product for more than a decade, compared with at least 3% invested by technologically advanced nations such as Denmark, Japan and Sweden. Koul is nonetheless optimistic, and has helped to forge a collaboration between IMTECH and Johnson & Johnson, announced in August. They will work in parallel on four new molecules as potential drug targets and explore shorter, safer and more-effective oral treatment regimens for various strains of TB. Biopharma strides Koul’s collaboration is well placed to take advantage of the success of India’s pharmaceutical industry. Building on the solid foundations of the country’s expertise in academic chemistry, major pharmaceutical companies have set up factories to make affordable generic antibiotics, vaccines, and diabetes and HIV medicines. This strength is paying dividends. According to Hyderabad-based Sathguru Management Consultants, India’s pharmaceutical industry was worth US$18.8 billion in 2010 and $41.1 billion in 2017, and is expected to expand to an estimated $72.4 billion in 2022. One-fifth of the world’s generic drugs are made in India, and around half of this manufacturing is based in Hyderabad. The production of generics has certainly helped the sector, but many people hope to see the country grow beyond manufacturing. “We now need to be recognized for new drugs that address unmet medical needs,” says Kiran Mazumdar-Shaw, managing director of biopharmaceutical company Biocon in Bangalore. The firm’s growing pipeline of biologics ranges from oral insulin for diabetes to monoclonal antibodies for use in cancer therapy. “There is incredible potential within India to become a powerhouse driving biopharma innovation in the Asian market,” says Vaz Narasimhan, himself a second-generation Indian American and chief executive of Novartis, a pharmaceutical company in Basel. The biopharma industry is increasingly looking for new types of talent, says Narasimhan. He gives the example of data analysts and mathematicians who he says are driving the next wave of medical innovation. Meenakshi Diwan works on a solar panel in India’s Odisha state in 2009 — then part of a burgeoning solar grid with a capacity of less than 10 MW. Now, India has a solar capacity of more than 6,000 MW.Credit: Abbie Trayler-Smith/PANOS Narasimhan’s confidence in Indian pharmaceutical development is significant. Most pharma companies have been reluctant to take on costly research and development to combat ‘poor-man’s diseases’ such as malaria and TB, says Soumya Swaminathan, one of India’s leading experts on TB. Swaminathan was appointed deputy director-general for programmes at the World Health Organization in October. She has led an effort to consolidate India’s fragmented TB research, previously supported by four separate institutions, under one umbrella organization — the IndiaTB Research Consortium. “These diseases are our problem,” she says. “And it is pointless expecting Western pharma companies to be interested in them.” When asked, Indian pharmaceutical companies say they are reluctant to take up research in these areas, citing a lack of government funding for early-stage research, and reams of red tape once a product reaches clinical trials. Pollution pains In April, a collaboration between researchers in Germany and Anil Dayakar, an environmental activist in India, reported that Hyderabad’s pharmaceutical manufacturing was polluting the region’s water system to an “unprecedented” degree, and hurrying the development of drug-resistant forms of bacteria (C. Lübbert et al. Infection 45, 479–491; 2017). The researchers suggested that more regulation was needed to prevent further pollution in the region. The pharmaceutical industry in India is not the only source of contamination — pollution is common to many of the country’s cities, and India’s capital, New Delhi, spends its winters wrapped in smog. Krishna Ganesh, director of the Indian Institute of Science Education and Research in Tiruptai, hopes that science can help. “The focus in chemistry is now shifting into areas that involve green and sustainable chemistry,” he says. Research topics include non-toxic chemicals, environmentally benign solvents, organic production and renewable materials. “The main aim should be to get rid of toxic chemicals produced in industrial manufacturing,” and to prevent gases escaping into the atmosphere, he says. Nanotech hopes India’s strength in chemistry has aided its effort to become a leader in the interdisciplinary field of nanotechnology. It’s an especially tempting area of research because there’s a deep vein of funding to mine, says Kizhaeral Subramanian, a researcher in the department of nanoscience and technology at Tamil Nadu Agricultural University in Coimbatore. “Global funding for nanotech had increased from $1 billion in 2000 to $2 trillion in 2016,” he explains. On top of that, Subramanian says that the country has a strong talent pool to draw from owing to the proliferation of nanotechnology degree programmes across the country. From a developmental perspective, the field is a sensible focus as well. As India’s population swells further, the demand for food and clean water is rising. “Nanomaterials can help in water cleansing from bacterial and metal contaminants,” says Ganesh, and nanomaterials may also be able to help with crop protection. For example, Tamil Nadu Agricultural University is researching the production of non-toxic herbicides and fertilizers, as well as emulsions and films that improve the shelf life of fruits and vegetables. Energy dark holes Of India’s 1.3 billion citizens, almost 20% still lack electricity. To help combat this, the country has launched an ambitious renewable-energy plan, broadly focused on solar and wind power. Overall, the country hopes to produce 175 gigawatts from renewable energy sources by 2022 — meeting around 20% of the country’s predicted electricity demand. According to Tata Narasinga Rao, associate director of the International Advanced Research Centre for Powder Metallurgy and New Materials in Hyderabad, India enjoys between 250 and 300 clear sunny days each year — ideal for solar technologies. The energy plan is helped by cheap land, a vast pool of talent to draw from and enthusiastic government support and infrastructure, says Rao. In a review published this year, the International Renewable Energy Agency lists India among the six countries — with Brazil, China, Germany, Japan and the United States — that accounted for most of the renewable-energy jobs in 2016. One research programme, the Solar Energy Research Institute for India and the United States, brings together the Indian Institute of Science in Bangalore and the National Renewable Energy Laboratory in Denver, Colorado, to accelerate the development of solar electric technologies by lowering the cost of production. As part of this venture, scientists developed a new nanotechnological solar absorption system in 2015. The prototype, Rao says, costs half as much as the non-vacuum tubes currently used in solar collectors worldwide and have enormous potential for industry. There are local quirks to take into account before any company starts cashing in on a solar goldmine. Manufacturers still haven’t worked out what to do about monkeys and rats, which relentlessly and indiscriminately chew telephone, electrical and fibre-optic cables across the subcontinent. Meanwhile, Indian researchers are using crop residues, normally burnt as waste by farmers, to develop advanced biofuel systems and products such as biogas and biomaterials. “India’s strong knowledge base in biotechnology, chemistry, engineering and process engineering can be tapped to do research in the biofuel sector,” says Ahmad Kamal, a chemist at the Indian Institute of Chemical Technology in Hyderabad. Calling young scientists back To achieve its grand ambitions, India needs to nurture its new-found brain gain, and is fighting to make itself as attractive as possible through the Department of Science and Technology (DST), one of India’s largest research-funding agencies. In June, for example, the DST announced endowments of $10,000 a month for researchers who choose to move to India from labs overseas. Lipi Thukral, a computational biologist at the Institute of Genomics and Integrative Biology in New Delhi, thinks that the Indian research sector has been unfairly stereotyped abroad. “It is a myth that Indian salaries for scientists are low. They are very good when one factors in the purchasing power of the rupee,” she says. “One can do great science here, too.” Thukral uses high-performance computers to study the movement of biological structures and to model protein folding. After a PhD in Germany, and a postdoc in the UK, she returned to India in 2012 under another DST scheme. Shalini Gupta, a chemical engineer at the Indian Institute of Technology Delhi, returned to India in 2009 after earning a PhD in chemical and biomolecular engineering from North Carolina State University, in Raleigh, and a postdoc from Imperial College London. Gupta’s team is working on cheap, portable medical tools to rapidly diagnose sepsis, a serious complication of many bacterial infections. For her, India makes the perfect laboratory. “We have the advantage of having ready access to patients, samples and field trials.” Meanwhile, the Indian government plans to develop 20 existing universities into ‘world class’ research institutions with an incentive of $1.54 billion of funding. Policymakers hope this will free the country’s best universities from reliance on the country’s grant commission and associated red tape, and encourage greater institutional autonomy. “There are always challenges in working in a third-world country, but India’s role in the development of next-generation technology cannot be ignored, especially in the fields of pharmaceuticals, agriculture, energy and environment,” says Gupta. “If you are situated close to a problem, you have a bigger advantage in terms of solving it.” Nature 552, S41-S43 (2017) doi: 10.1038/d41586-017-07771-y