NEWS FEATURE

Singapore’s multibillion dollar gamble

How does a country one-fourth the size of Rhode Island with little history in biomedical science become one of the world’s biomedical research giants? The answer: with a pile of money and a large dose of chutzpah. Since 2000, has dumped more than US$2 billion into developing a biomedical research industry—from scratch. Is the gamble paying off?

A matter of life and death plan masterminded by Yeo and hashed Science is a notorious example of what out in an all-night session with three of economists call “increasing returns to Singapore’s top doctors, Tan Chorh scale”—groups of productive people Chuan, then Dean of Medicine at the feed off each other to create something National University of Singapore (NUS), that is more than the sum of its parts. and oncologists John Wong and Kong The reverse is also true: isolated indi- Hwai Loong—a group Yeo refers to as viduals will have a hard time generating the “biomedical sciences ‘Gang of 4.’” momentum and are less productive. So Although the idea met with considerable how can you get a new hotbed of skepticism, says Yeo, the government research started in a country with a eventually (and reluctantly) gave him the limited history of biomedical research? green light. The plan was announced in Biopolis, Singapore’s futuristic research hub. In the 40 years since gaining inde- 2000—one day before the unveiling of pendence, Singapore has become one the human genome project—and de- The personnel payoff of the wealthiest nations in the Asia voted nearly US$2 billion over five years Thanks to Yeo’s aggressive recruitment Pacific region. Per capita income, for to the development of public and private efforts, Singapore is now home to a bevy example, has increased an average of sector biomedical research. of acclaimed scientists. Among them are 6.4% per year from 1965 to 2000. Yet For the government, failure of the Sir David Lane, discoverer of the p53 that growth has been driven largely by BMSI is not an option. “When we say tumor suppressor gene, who is serving a manufacturing rather than knowledge- that Singapore is serious about science, two-year stint as the Executive Director based industries. Singapore realized it we are dead serious,” said Second Minis- of the Institute for Molecular and Cell had to make a change. ter for Trade and Industry Vivian Bal- Biology (IMCB), and Edison Liu, former That change came in the late 1990s akrishnau in his opening remarks at an head of the Division of Clinical Sciences with the decision to emphasize knowl- October 2005 Keystone symposium on at the National Cancer Institute (NCI) in edge industries, including biomedical stem cells, senescence, and cancer—the the US, who became the Executive science. The decision was spurred in first Keystone meeting to be held outside Director of the Genome Institute of part by the worldwide electronics North America. “For Singapore, success Singapore (GIS) in 2001. slump, which drove jobs in the elec- is a matter of life and death.” Japanese cancer researcher Yoshiaki tronics industry—a mainstay of the Ito, who identified RUNX3 as a tumor country’s economy—to cheaper loca- “When we say that Singapore suppressor gene associated with stomach tions in Asia. And with no natural re- is serious about science, cancer, relocated to the IMCB in 2002— sources to bolster the country’s we are dead serious.” with his entire laboratory staff in tow— economy in times of hardship, Singa- -Vivian Balakrishnau, Second Minister after reaching Japan’s mandatory pore needed other options. “The Sin- for Trade and Industry university retirement age of 63. Also on gapore economy needed to diversify, board is molecular biologist Alan Col- to become like a table with many Yeo immediately set out to lure some man, formerly with PPL Therapeutics— legs,” says Philip Yeo, Chairman of of the world’s best scientists to Singapore. the Scotland-based pharmaceutical Singapore’s Agency for Science, Tech- The idea was that top-tier scientists will company that cloned Dolly the sheep. nology, and Research (A*STAR). help make Singapore a more enticing Colman, who received a S$6 million “The additional leg of biomedical option for the junior faculty, postdocs, grant to relocate to Singapore, is now science would stand us in good stead and students required to get the coopera- chief scientific officer of ES Cell Inter- in riding the next big wave.” tive machinery of science up and run- national, a government-owned biotech This need to diversify spawned the ning. “It’s a circle,” says Kong Peng Lam, company that is developing human em- Biomedical Sciences Initiative (BMSI), a Acting Executive Director of A*STAR’s bryonic stem cells for disease therapy. Biomedical Research Council (BMRC), Nobel laureate Sydney Brenner, a Text by Heather L. Van Epps “If you get the best to come here, they long-time advisor to the Singaporean JEM News Editor; [email protected] will attract the best. It’s like a magnet.” government (he served as Chairman of

JEM © The Rockefeller University Press $8.00 1139 Vol. 203, No. 5, May 15, 2006 1139–1142 www.jem.org/cgi/doi/10.1084/jem.20060895 nity to conduct science in a less restric- tive environment than in the US. Indeed, whereas the US NIH frowns upon scientists’ involvement in the private sector, Singapore’s A*STAR does just the opposite. Knowing that successful biotech companies generate both revenue and jobs, the government encourages researchers to apply for patents and, based on those patents, to launch biotech start-up companies— offering three-year leaves of absence and S$150,000 in seed money as incentive. The free-flowing money is also part of Singapore’s allure for younger scien- tists, along with the potential for up- Philip Yeo, Chairman of A*STAR and driving force for Singapore’s biomedical science initiative. ward mobility. “Because we are at ground zero,” says Lam, “there are Singapore’s Scientific Advisory Board since Singapore gained independence. many opportunities [for young scien- from 1987 to 1997), is now Chairman of But for those already in Singapore, tists] and many positions available.” the BMRC. Brenner splits his time be- the scientific bounty clearly outweighed A good example of this upward tween Singapore and the Salk Institute the cultural drawbacks. And with re- mobility is Thomas Dick, Head of the for Biological Studies in San Diego. searchers in the US and Europe com- tuberculosis group at the In- If you ask what attracted these scien- plaining that funding is becoming stitute for Tropical Diseases, who tific heavy hitters to Singapore—a coun- increasingly difficult to secure, the stellar moved to Singapore in 1990 when try with a steamy climate, authoritarian reports from Singapore’s expats—along biomedical research was still in its in- government and a notoriously Draconian with the no-strings-attached money given fancy. Fresh out of graduate school at penal code—you’re likely to get a variety to new principal investigators (PIs)— the University of Heidelberg, Dick of answers. But the common denomina- might prove too tantalizing to pass up. heard that the newly founded IMCB tor seems to be the “vision of Philip This was true for two of the most was looking for postdoctoral fellows Yeo”—a phrase heard with an almost recent defectors to Singapore: cancer and thought “why not Asia, why not eerie regularity in Singapore. In fact, the geneticists Neal Copeland and Nancy the tropics for a couple of years?” universally glowing reports from Singa- Jenkins, who recently relocated to Singa- Six years later, when the time came pore’s expat scientists (along with pore’s IMCB from the US NCI. In ad- for Dick to venture out on his own, he A*STAR’s apparently strict requirement dition to the funding crunch in the US, questioned whether to stay in Singapore for scientists to obtain permission before the duo cite restrictions on stem cell speaking to the press) leave one wonder- research and frustration with National ing if the picture is a bit too rosy. Institutes of Health’s (NIH) new ethics policy—which forbids NIH employees “If you get the best to from consulting for or holding financial come here, they will attract the best. interests in private companies—as part of It’s like a magnet.” the impetus to end their two-decade- -Kong Peng Lam, Acting Executive long stint at the NCI. Director of the BMRC “It also helps to have a lot of money,” says Copeland. “We didn’t even negoti- But the few complaints one can ate a budget [at IMCB], we just told coax out of Singapore’s imported sci- them how many people and how many entists tend to be cultural rather than mice (thousands of cages)…then sent scientific. The government’s fear of them a list of equipment we needed.” criticism, for example, has dampened The husband-and-wife team—who artistic expression, meaning that Singa- developed a technique to accelerate the pore’s cultural scene doesn’t measure identification of cancer-causing genes in up to that of most cosmopolitan cities. mice—turned down offers from Stanford Others are put off by the lack of politi- University and Memorial Sloan Ketter- cal opposition to the ruling People’s ing Cancer Center in New York, opting Action Party, who have been in power instead for what they saw as an opportu- Microarray facility in Biopolis.

1140 SINGAPORE’S MULTIBILLION DOLLAR GAMBLE | H.L. Van Epps NEWS FEATURE

IMMUNOLOGY PICKS UP SPEED Singapore may have lagged behind other countries in This solid financial sup- the immunology arena in recent years, but they’re now port helped convince Paul trying to make up for it. The immunology program at MacAry, an Assistant Profes- the NUS—still in its infancy at a mere two years old—is sor in the Immunology pro- headed by Michael Kemeny, an allergy expert who was gram, to join Kemeny in recruited in 2004 from King’s College Hospital in Lon- Singapore. “The start-up don. Although King’s College was then being made into package I was offered was a national center for allergy and immunology (along with significantly better than those Imperial College London), Kemeny was enticed by the from UK and US institu- idea of launching a new program in Singapore. tions,” says MacAry, whose The fledgling program, which currently has 16 full and offer included not only re- 14 associate members drawn from various departments and search funds and a competi- institutes at NUS and Biopolis, will be expanding its ranks tive salary, but also subsidized in the next few years, with faculty positions available at the living accommodations and full, associate, and assistant levels. an education allowance for On offer for those considering a move East are the his children. program’s lavish new digs in the refurbished IMCB But MacAry was initially building (where it will relocate later this year), a collaboration- skeptical. “As a postdoc in the friendly research environment and an outstanding start-up UK,” he says, “there is a package. “Within 1-2 years of coming to Singapore,” says general consensus that the US Michael Kemeny (top) Kemeny, “new PIs typically hold up to S$1 million of and Europe are the only places and Paul MacAry. competitive funding.” where you can establish yourself as a good biomedical Kemeny also stresses the program’s proximity to a researcher.” On top of that was concern about feeling medical school and tertiary referral hospital, and its access isolated as one of only a small number of immunologists in to investigators across a multitude of disciplines—among Singapore. He now thinks those fears were unfounded. them computational biology, epidemiology, neuroscience, MacAry, who moved to Singapore with his wife and microbiology, pharmacology, imaging, bioengineering, young children, also praises Singapore as a safe and child- structural biology, and stem cell biology—which breeds a friendly place with a world-class education system. unique collaborative environment. “No other group in With enthusiastic salesmen like Kemeny and MacAry Singapore is able to work so closely with so many different and plenty of cash to import and train new talent, the specialities and experts,” says Kemeny. immunology program seems poised for success.

or return to Europe. “As it turned out,” rate partnerships. derway and is targeted for completion he says, “this step was quite easy here in For top-notch research facilities, at the end of this year. Also under con- Singapore, and the lab head position was one need look no further than Biopolis, struction is phase 1 of a 390,000- attractive: it came with funding!” Since a futuristic two-million-square-foot square-foot center for physical sciences then, Dick has risen through the ranks biomedical research complex that called Fusionopolis, slated for comple- from Laboratory Head to Assistant Pro- houses the sparkling new laboratories of tion in mid-2007. fessor to Associate Professor in regular A*STAR’s five research institutes plus Pharmaceutical and medical technol- three-year intervals. dedicated space for biotech start-ups ogy companies are also setting up shop in and pharmaceutical companies—not to Singapore. Pharma giant GlaxoSmith- Recipe for success mention restaurants, a day care center, Kline (GSK) first entered with bulk man- Although biomedicine in Singapore fitness center, pub, and even a 7-Eleven ufacturing facilities. It recently launched a seems to be off to a flying start, the convenience store. Biopolis—which preclinical research facility for neurode- country will need more than just man- went from concept to reality in an aston- generative diseases, the first such facility power to ensure that their costly gamble ishing 20 months—was designed to in the Asia Pacific region, and its next in- pays off. To succeed, Singapore needs foster cross-disciplinary collaboration vestment in Singapore will be a US$70 to turn basic research into revenue—a and bridge the gap between academic million R&D pilot plant dedicated to feat that will require other ingredients, and industrial research. converting experimental molecules into including state-of-the-art facilities, sup- Construction of Biopolis Phase 2, commercially viable drugs. Schering port for manufacturing and research which will add another 120,000 square Plough, Merck, Pfizer, and Eli Lilly also and development (R&D), and corpo- feet of research space, is currently un- have active subsidiaries in Singapore.

JEM VOL. 203, May 15, 2006 1141 In 2004, Swiss pharmaceutical com- government, whose financial commit- pected to follow this year. A*STAR is pany Novartis teamed up with the ment to biomedical research has been also fishing out younger students with Singaporean government to create the unwavering. its new Young Researchers Attach- Novartis Institute for Tropical Diseases, On the heels of the initial BMS Ini- ment Program, in which pre-university which is focused on studying neglected tiative comes the Science and Technol- students from around the globe study tropical diseases such as Dengue fever and ogy 2010 Plan, announced in February at Singapore’s secondary schools and drug-resistant tuberculosis. Singapore’s of this year, which will commit another junior colleges, spending vacations on biomedical initiative is also bolstered by US$5 billion over five years toward bol- stints at A*STAR’s research institutes. partnerships with overseas universities in- stering public and private sector R&D. Those that do well are then eligible for cluding Stanford and Johns Hopkins uni- With its chunk of the change, the A*STAR scholarships. versities in the US, Sweden’s Karolinska BMRC will focus on translational re- Institute, and Japan’s RIKEN Institutes. search with the hope of turning basic Whereas the US NIH frowns upon Singapore’s collaborative approach research discoveries into clinically useful scientists’ involvement in the to science is beginning to bear fruit. and commercially viable products. private sector, Singapore’s A*STAR One example is the recent develop- But money alone will not ensure does just the opposite. ment of a diagnostic kit for avian influ- success. According to Yeo, the most enza (H5N1). The kit, developed by important elements for maintaining As with his recruitment efforts, Yeo local start-up company Veredus Labo- momentum in the biomedical sciences sets the education bar high. Those who ratories Pte Ltd using nucleic acid are “two-legged ones, people!” Indeed, are funded are allowed only three years primers designed at A*STAR’s GIS, Singapore needs to maintain a critical to complete their undergraduate degree allows for rapid, accurate diagnosis of mass of scientists, preferably while less- and five for their Ph.D. training—all human cases of avian flu and is cur- ening its reliance on imported talent— while maintaining a 3.8 GPA. “When rently being used in Indonesia. currently about one third of all scientists you first start out at 18 years old,” says But the real question is whether the in Singapore are foreigners. To do this, Pearline Teo, an A*STAR scholar who biomedical science push is translating into Singapore has begun to nurture its own earned her undergraduate degree in bi- jobs and revenue. The answer, so far, is scientific workforce. Another brain- ology at Johns Hopkins University, “it yes. As of 2005, 10,200 people were child of Yeo, this endeavor involves a seems like a pretty tall order.” Teo, employed in the country’s biomedical complete revamping of the country’s who is now working toward a Ph.D. in science industry, a figure the Economic education system—from overhauling immunology at Stanford University, Development Board hopes will increase the primary school curriculum to of- says the GPA requirement is a source of to 15,000 by 2015. The biggest revenue fering scholarship programs that fund grumbling among her fellow A*STAR source so far is the bulk drug manufactur- undergraduate and Ph.D. science train- scholars, particularly at Stanford, where ing rather than the more recently estab- ing either locally or abroad—to bright only about 10% of the class receives an lished biotech sector. Biomedical Singaporean students. A grade. manufacturing output is also on the rise, This training comes with strings Perhaps the biggest hurdle that Sin- surpassing its 2005 target of S$12 billion attached: A*STAR scholars are com- gapore faces in revamping its education a year ahead of schedule. mitted to six years of research at an system is cultural. In a country where A*STAR research institute after gradu- education is notoriously rote and rigid, Keeping the ball rolling ating. More than 300 students are now it remains to be seen whether A*STAR Another part of keeping the biomedical in the Ph.D. pipeline, with the first students will measure up in terms of ball rolling is keeping the money flow- eight scholars completing their Ph.D. scientific creativity. As the first crop of ing—a nonissue for the Singaporean training in 2005 and another 18 ex- Ph.D. graduates are just now returning to Singapore, only time will tell. Former Singapore Prime Minister famously stated that air conditioning was the most important invention for lifting tropical developing countries out of their heat-induced lethargy. Now, Singapore is taking the next step—attempting to make the in- venting process itself an integral part of the economy. Yeo, for one, is betting on success. “We have the funds, single- minded focus, long-term planning, and industrial investment experience—and Biopolis boasts a complete “work–live–play” atmosphere. the daring to go for it.”

1142 SINGAPORE’S MULTIBILLION DOLLAR GAMBLE | H.L. Van Epps