It was her beer-brewing know-how that helped make Kiran Mazumdar-Shaw the richest woman in India and sparked a mini biotechnology boom in the country's information-technology capital: her native city, Bangalore.
In 1973, after earning a degree in zoology from Bangalore University, Shaw headed to Australia to study brewing. But work as a brewmaster was hard to find — and being a woman didn't make it any easier. Shaw fortuitously connected with an Irish firm — Biocon Biochemicals — and agreed to start a joint venture in Bangalore in 1978, initially manufacturing enzymes.
"I almost started on the rebound," says Shaw. She was an industry neophyte, but her training in using enzymes to craft the perfect pint provided a robust bridge for her move from beer to biotech. It worked well. In 2007 the company raked in revenues of around US$249 million, a big increase over previous years due in large part to Biocon's sale of its enzyme business to concentrate on pharmaceuticals. Mazumdar-Shaw still has a large stake in Biocon, which is now a publicly traded company.
S. RAYMER/CORBISBut even Biocon is still trying to establish itself as a master practitioner of discovery science. At present, most science, engineering and technology jobs in Indian companies emphasize rote tasks rather than encouraging innovation and discovery. Biotech and pharmaceutical companies throughout India are trying to change that (see Nature 450, 580; 2007). The heart of this effort lies in Bangalore, which boasts not only a strength in biotech but a tradition in academic science that stretches back nearly a century. Scientists in industry and academia are trying to recruit and retain top talent, while finding ways to spark innovation.
Arriving in Bangalore, it's not the plethora of IT companies, nor even the sun and the palm trees, that make the greatest impression. It's the traffic. Rickshaws, motorbikes and bicycles weave in and out of the cars in what looks like controlled chaos. Trips that should take 20 minutes take more than an hour. Clearly, this is a city whose infrastructure is ill-equipped to handle the tremendous growth of the past decade.
Tortuous paths
Biocon boss Kiran Mazumdar-Shaw has discovery science as her goal.BIOCONA career path in basic research and biotech in India can be equally circuitous. For example, Balasubramanian Gopal, now a young professor at the Indian Institute of Science (IISc) in Bangalore, earned a master's in physics at the Indian Institute of Technology in Kanpur before finding a job in pharma at Torrent Pharmaceuticals in Ahmedabad. He then headed back to school at the IISc for a PhD focusing on structural biology and over to Britain's National Institute of Medical Research for a postdoc in crystallography. Akhilesh Pandey left a sought-after position as a physician in the Indian armed forces to pursue biomedical research in the United States and India (see 'Grand designs'.).
Hosahalli Subramanya, now a vice-president at Bangalore-based Aurigene, a biotech services company, took a risk on Bangalore biotech. After a PhD at the IISc he moved to the University of Oxford, UK, where he completed two postdoctoral stints before returning to India to work for the government-run Central Drug Research Institute at Lucknow. Coming to Aurigene as one its first employees 6 years ago was a gamble. "I had good funding," he says. "And I had offers from other places." Luckily, his move paid off.
Upstart biotechs follow inBangalore's long tradition of academic science, notably the National Centre for Biological Sciences, a small but prestigious institute on the campus of Bangalore's University of Agriculture. And then there's the IISc, founded nearly 100 years ago by entrepreneur Jamsetji Tata, who also started the multinational Tata Group of companies. The institute has divisions in biological, chemical, physical, mathematical and electrical sciences. And, with increasing government support and its centenary approaching, it plans new buildings for aerospace, biological sciences, information sciences, physical sciences and a centre of excellence in nanoelectronics.
Recruiting talent
The IISc is incredibly selective. Each year about 2,000 students take the IISc entrance test for biological sciences. About 250 are called for interview and 10–12 are admitted as graduate students in each of the five biosciences departments. Even so, the IISc, in common with other Indian institutions, faces a problem: those who demonstrate exceptional talent often leave to pursue a career in the United States or Europe.
Concern about the brain drain prompted the institute to devise an integrated PhD programme that accepts promising undergraduates directly into a PhD, skipping the master's degree, and funds them. IISc chair of biochemistry D. N. Rao admits success has been mixed. Some students have left the PhD programme after the first two years to do a doctorate overseas, taking their newly acquired IISc-sponsored training with them. The shorter graduate training times can also stunt research creativity, says Rao, as investigators work on less risky, more short-term projects because they cannot bank on students devoting many years to the problem. However, the IISc's reputation and Bangalore's increasing global visibility in recent years have started to attract visiting students and new faculty to the campus.
New beginnings: staff of the Institute of Bioinformatics, Bangalore.A. PANDEYDespite the tough competition, graduate student recruits often lack important communications skills, says Gopal. Many come originally from villages and have poor English, the accepted language of science in India. "They have an inferiority complex, and keep quiet," he says. "But when you actually look at them at the bench, you say 'wow'." Gopal calls them the "H1B missed" generation, referring to the visa required to work in the United States. They have neither the language skills nor the funding to go abroad.
Well-qualified people are needed by a biotech sector that is still recruiting. Subramanya says Aurigene plans to take on 60–70 employees in the next few months on top of the 250 scientists it already has. He says some specialist positions will be difficult to fill. The bustling IT sector also competes for talent, especially for entry-level positions with a computer-skills component. The strategy of contract-research giant Quintiles Transnational, in Bangalore since 1997, is to recruit college graduates in the pharmaceutical and life sciences and train them to process clinical research data and arrange clinical trials for big pharma clients.
" As a country of 1.2 billion, we still haven't made our own drug. That still drives me. "
Balasubramanian Gopal
Taking a risk
But the biggest challenge facing Bangalore biotechs is to establish a culture of innovation and invest in higher-risk discovery research. Subramanya believes that the stigma that India can do only copycat research is no longer there. Six years ago, Aurigene would be expected to just make a given compound, he says. Now the company has more of an R&D focus — trying to attack a target with a compound that has the right properties to be effective. Laws passed in 2005 have made it easier to protect intellectual property in India, a crucial step to curing the private sector of risk aversion.
At Biocon, Mazumdar-Shaw says discovery science is a major goal, as is collaboration with the area's much smaller biotechs. She claims that the company has fared so well because of its capacity to expand and evolve its repertoire — from enzymes to biopharmaceuticals and monoclonal antibodies. Mazumdar-Shaw, a member of a special panel of the Indian government's Department of Biotechnology working to reform bioscience in the country, says schooling will be key. Specialist training before going into industry and management training as part of biotechnology education are both in the works. "As a country of 1.2 billion, we still haven't made our own drug," says Gopal, downplaying generics and herbals. "That still drives me."
Grand designs
In 1990, Akhilesh Pandey was a promising physician, having graduated from India's prestigious Armed Forces Medical College in Pune. But he convinced his parents to help pay the fee releasing him from his 20-year bond of service in the Indian armed forces. They had to sell their car to do so. Pandey had decided that basic research was his real passion, and his parents trusted his instincts. Twelve years later he would gamble again, in the hope of establishing an independent non-profit scientific institute in India, a rarity in the country.
After securing his exit, Pandey headed to the University of Michigan to get his PhD and then finished his residency at Brigham and Women's Hospital in Boston, Massachusetts. He followed that with a postdoc at the Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, and a visiting-scientist position at the University of Southern Denmark in Odense. It was during his time at Johns Hopkins School of Medicine in Baltimore, Maryland, where Pandey is still an associate professor, that he devised his ambitious plan for a bioinformatics institute.
Pandey envisaged an Institute of Bioinformatics and wanted it to be in Bangalore. The primary project would be a huge human protein database, with information on protein interactions, modifications and roles in disease. Again his family came to his aid. Pandey got loans from his brother and parents, and maxed out his credit cards. His Human Protein Reference Database was sustained by a grant from the US National Center for Biotechnology Information, under the auspices of the National Institutes of Health (NIH) in Bethesda, Maryland.
Six years later he has been able to pay back his family, but not himself — and there are no guarantees of the institute's future. Expansion is difficult because lenders in India are wary of an institute lacking steady government or venture-capital backing. Pandey had to convince his own lawyer that the institute wasn't a way to surreptitiously launder money.
At its peak, the institute had 70 employees; it now has 50 since losing funding as a result of the NIH's budget cuts. Nevertheless, Pandey, who splits his time between Johns Hopkins and the institute, plans to construct a mass spectrometry facility as well as a community-driven proteomics initiative called Human Proteopedia. "We want to spoil the user," he says. Now that the institute has proved its bioinformatics mettle, he and his colleagues are seeking new grants. He is optimistic that the institute can flourish — and that he'll be able to pay off the last of his debt.
G.R.
