by Tng Ying Hui
Under A*STAR, new biomedical research institutes were set up and housed in a 2 million sq ft edifice in Buona Vista, built in 2003. Comprising seven buildings, all linked together by hanging glass bridges, it was named the Biopolis, as suggested by Dr Brenner. Today, corporate laboratories of Singapore and international biotechnology companies, and the biomedical research institutes are co-located there to encourage the exchange of ideas and collaboration.
Dr Brenner has been vocal with his views on how biomedical research should be funded. Applied and clinical research, which seeks to turn discoveries into commercial applications or patient treatments, is important. But so is “discovery science” or basic research, which is the quest for new knowledge and investigation of the unknown, he argues. He said, “You’ve got to fund the whole spectrum from the very basic to the very applied. If you fund the clinical work separately, it is of poor quality.”
In the last decade, Dr Brenner has been devoted to redressing what he feels is an “Asian disease”—the hesitation that Singaporeans have in asking questions and challenging authority. In an interview with The Straits Times in 2007, he said that Singapore’s “young scientists are not cheeky enough; they do not ask questions”. The response from the journalist, he recounted in an interview for this book with a twinkle in his eyes, was, “How do we teach them to be cheeky?”
While Singaporeans possess many positive attributes, including the drive and motivation to upgrade themselves, there are other qualities that are essential to innovation, he said. “Science only progresses because authority is questioned. Go and have a look at the life of Galileo,” he said, referring to the Italian astronomer and mathematician who is known as the father of modern science and physics.
In 2009, Dr Brenner founded the Molecular Engineering Lab (MEL) as an laboratory for young Singaporean scientists, to have free rein to pursue their ideas and embark on projects that they are interested in. There are just over 10 researchers—“a radical group, though not in the political sense”, he said—comprising mostly returning A*STAR scholarship holders. At MEL, they meet with Dr Brenner to discuss their ideas and describe how they intend to develop their research programmes. Said Dr Brenner, “It is very not Singaporean to have an open lab, but it is the way I learnt to do science.” He believes that a top-class scientist must be good both at questioning and at doing things. Said Dr Brenner, “It is the combination of ideas and then going right through brick walls when you have to.” For his contributions to Singapore, Dr Brenner was conferred the Honorary Citizen Award in 2003. In 2006, he was awarded the National Science and Technology Medal. He also has an orchid named after him—the Dendrobium Sydney Brenner.
References
Errol C. Friedberg, Sydney Brenner: A Biography (New York: Cold Spring Harbor Laboratory Press, 2010).
Carolyn Khew, “Mentor to a Nation’s Science Ambitions”, The Straits Times, September 25, 2015.
Kash Cheong, “Trailblazing Biomedical Research Facility Turns 30”, The Straits Times, May 11, 2015.
Nicolas Wade, “Fish Genes aid Human Discoveries,” The New York Times, July 26, 2002.
Parliament of Singapore, “Estimates of Expenditure for the Financial Year 1st April, 2000 to
31st March, 2001,” March 11, 2000.
Parliament of Singapore, “National Science and Technology Board: (Amendment) Bill,”
August 27, 2002.
Sheo S. Rai, “Overview of the BMS Industry,” APBN 10 (2006),
http://www.asiabiotech.com/publication/apbn/10/english/preserved-docs/1008/0404_0406.pdf.
Tharman Shanmugaratnam, “Speech by Deputy Prime Minister and Minister for Finance,
at the Launch of GSK's New Global Headquarters for Asia,” March 11, 2015
http://www.mof.gov.sg/news-reader/articleid/1475/parentId/59/year/2015?category=Speeches
Interviews with Dr Sydney Brenner in March and October 2015.
Dr Sydney Brenner
South Africa b.1927
Prof Edward W. Holmes
Bringing Research from Bench to Bedside
US-born Prof Edward Holmes’ stellar reputation and wide network contributed to Singapore’s rapid growth in its capabilities in translational clinical research, encouraging companies from abroad to forge partnerships with the local scientific community.
Singapore launched its biomedical sciences initiative at the turn of the 21st century and by 2006, its next push was to build up its competency in translational and clinical research (TCR). Such research develops discoveries made in the laboratory into new ways of treating patients and health products; basically, developing lab innovations to the point where the medical sector or healthcare agencies find it attractive to further develop these innovations.
Professor Edward Holmes was called on to be one of the architects of Singapore’s TCR infrastructure. Currently, he is emeritus vice-chancellor and dean of the medical school at the University of California, San Diego (UCSD), has spent his entire career which spans more than 40 years, building up the United States’ TCR capabilities. He has held senior administrative positions at Duke University, Stanford University, and University of Pennsylvania.
Prof Holmes was no stranger to Singapore. He was appointed to the International Advisory Panel for the NUS’ Graduate School for Integrative Sciences and Engineering in 2003. During one of his trips here in 2006, he met then-Chairman of A*STAR Philip Yeo who, as Prof Holmes recalled, asked, “Why don’t you work in Singapore?” In response, Prof Holmes half-jokingly said, “Why don’t you make me an official offer?”
Within three days, Prof Holmes received a job offer to be the executive chairman of the National Medical Research Council (NMRC), and the executive deputy chairman of the Biomedical Research Council (BMRC). The NMRC comes under the Ministry of Health (MOH) and oversees the development and advancement of medical research in Singapore. The BMRC was set up in 2000 to support, oversee and coordinate public sector biomedical R&D activities. His wife, Judith Swain, one of the world’s leading molecular cardiologists, was also offered a position as executive director of the Singapore Institute of Clinical Sciences at A*STAR. She held this position until 2014 when she became a senior fellow at A*STAR.
Within three months of Prof Holmes accepting the offer, he came to Singapore. Shortly after arriving, he and the deputy chairman of A*STAR, Professor Tan Chorh Chuan, sat down in Prof Holmes’ unfurnished apartment and charted the first draft of Singapore’s roadmap for translational research. “That was our first draft,” Prof Holmes said. Over the next few months, he would work with colleagues from the biomedical field to firm up the grant structures that would enable TCR for the next five years.
Prof Holmes surmised that the missing puzzle piece in Singapore’s biomedical industry at that time was a shortage of clinician-scientists—individuals who conduct biomedical research and have a thorough understanding of how these discoveries could improve human health. “They are the magic ingredient in biomedical research,” said Prof Holmes. Individuals who are both physicians and scientists take a lengthy process of more than 15 years to complete their medical and post-graduate degrees. As a result, few are willing to pursue this career track.
As a physician-scientist himself, Prof Holmes understood what scientists in the field needed. Clinician-scientists rely on grants as their main source of salaries and research support, but there were few grant mechanisms for them in Singapore, he said. To create a pool of talent, Prof Holmes helped devise the STaR Investigator Award to draw clinician-scientists from abroad and locally to conduct their research in Singapore.
Prof Holmes and Prof Tan also zoomed in on another problem: clinician-scientists tied up with their day-to-day duties of caring for patients do not have enough time to pursue research. The duo set up the Clinician Scientist Award to draw younger Singaporean clinician-scientists into the laboratories. Under this grant, doctors who have an established track record as researchers are given full funding for up to five years if they spend 70% or more o
f their time on research. Those who devote less time would have the funding quantum adjusted accordingly. As of mid-2015, more than 95 clinician-scientists have received awards from the NMRC, said the Ministry of Health. Said Prof Holmes, “NMRC has been successful in recruiting people and I am proud of the young scientists who have stepped up.”
Other than human capital, Prof Holmes and his colleagues saw that Singapore needed an environment that supported TCR. Most importantly, the MOH had to go beyond its role of managing the public healthcare system to encouraging medical research. Hospitals, medical schools and scientific institutes in A*STAR used to work independently but Prof Holmes encouraged the different bodies and agencies to support the idea of a new TCR infrastructure, build laboratories and collaborate in the research and delivery of drugs to patients.
Prof Holmes also worked closely with the Economic Development Board to encourage pharmaceutical companies to forge partnerships with Singapore’s scientific community. “We would meet with the chief scientific officer or CEO, describing to them the range of basic TCR available in the ‘ecosystem’ that’s here,” he said. “One of Singapore’s major advantages is the Asian phenotype. The three major ethnic groups here represent over 25% of the world’s gene pool,” he added. Although companies could set up shop in China or India, translational research had not caught on in those countries yet so Singapore proved to be a major attraction to the companies. With Prof Holmes’ help, the world’s largest biotech company, Roche, established a multi-million dollar medical research hub in Singapore in 2010 while in the same year the GSK Academic Centre of Excellence set up its first programme to enhance TCR by facilitating multi-disciplinary medical projects among A*STAR researchers, the universities and hospitals.
Prof Holmes was conferred the Honorary Citizen Award in 2011. He left his position at the NMRC in 2012 and held his position at the BMRC till 2014. Now a senior fellow at A*STAR, where he advises top administrators on research and acts as a bridge to others in the biomedical sciences community, Prof Holmes shuttles between San Diego and Singapore at least 10 times a year. He is also senior adviser to the National Research Foundation, an agency under the Prime Minister’s Office that coordinates all R&D. As Singapore is already at the stage of its biomedical initiative where collaboration with the private sector is expected to bear fruit, Prof Holmes believes that Singapore is on track to achieve its ambitions. “Before I retire, I hope we can see that there’s a made-in-Singapore drug in the clinic,” he said.
References
Joyce Hooi, “Roche to set up 100m Swiss Franc Research Hub Here,” The Business Times, January 29, 2010, https://www.healthxchange.com.sg/News/Pages/Roche-to-setup-100m-Swiss-franc-research-hub-here.aspx
Lim Chuan Poh, "GlaxoSmithKline Academic Centre of Excellence Awards 2010" (Speech at Economic Development Board, Singapore, October 7, 2010), http://www.a-star.edu.sg/Media/News/Speeches/ID/1357/GlaxoSmithKline-Academic-Centre-of-Excellence-Awards-2010.aspx
Ministry of Manpower,. 2011. Singapore Confers Prestigious Honorary Citizen Award on Professor Edward Holmes, http://www.mom.gov.sg/newsroom/press-releases/2011/singapore-confers-prestigious-honorary-citizen-award-on-professor-edward-holmes
Interview with Prof Edward Holmes over Skype in April and May 2015.
Prof Edward W. Holmes
United States of America, b.1941
Sir David Lane
The Conscientious Chief
UK-born Sir David Lane is set on grooming a generation of scientists with heart. In the cut-throat world of academia where most rush to publish, Sir David reminds his students of the importance of generosity and guards A*STAR’s research to ensure that there are no bogus scientific discoveries.
As the current chief scientist of A*STAR, what keeps Sir David Lane awake at night is the possibility of scientific fraud and the reputation of the organisation going down the drain. Recent scandals involving Japanese and Korean scientists have given Asian science a bad name. Sir David’s responsibility is to uphold A*STAR’s name and show that science in Singapore is just as robust as in the West.
Born in 1952, Sir David is best known for discovering the p53 gene, which he termed “guardian of the genome” as it protects cells from damage and helps prevent tumours. For instance, when cells are damaged during sunburn, the p53 gene causes these damaged cells to go into apoptosis and die. Without p53, abnormal cells proliferate, resulting in cancer. For this reason, the p53 is also called a tumour-suppressing gene. Sir David made this discovery while doing his postdoctoral work at the Imperial Cancer Research Fund in London after graduating with a PhD in immunology in 1976 from the University of London—where his supervisor, Professor Avrion Mitchison, described him as “the best student I ever had in college,” noted Professor Nikolai Zhelev from Abertay University in Dundee, Scotland, in an article on Sir David’s achievements. Sir David was knighted for his contributions to cancer research in January 2000.
In 2002, Sir David was invited to be chairman of the Scientific Advisory Board at the Institute of Molecular and Cell Biology (IMCB). But his daughter was still in high school and so he waited for her to enter university before moving to Singapore. In 2004, Sir David took up an appointment as executive director of the IMCB. He also took a two-year sabbatical, later extended to three years, from the University of Dundee, where he had been professor of medical oncology for 14 years. His wife, Prof Birgit Lane, an expert on the genetics behind human skin diseases, also took leave from Dundee to work at the Centre for Molecular Medicine as programme director. The centre is now known as the Institute of Medical Biology and she is its executive director. Scientific infrastructure was one of the considerations for their move. The facilities in Singapore make it easier to promote research, said Sir David. In Biopolis, scientists from different fields collaborate to work on projects that are difficult to do on one’s own. “There’s no place like this,” he added.
At IMCB, Sir David broke new ground in the study of the p53 gene. He developed antibodies that could target defective p53 genes in the zebrafish (a type of fish that is 70% similar to the human genome and often used as a biological model for scientists to experiment on) and discovered new forms of p53 that can control the gene’s work in suppressing tumours. The research could one day lead to a treatment for cancer. He also reviewed patents for approval at the IMCB. His task was to decide if they were worth filing. While the process is deceptively simple, it requires an understanding of specialist topics in science and knowing which invention would work and which would not.
In 2007, Sir David, with A*STAR’s support, set up the Experimental Therapeutics Centre (ETC), which aims to advance drug discovery in Singapore. A year later, he returned to Dundee University to head its new Division of Molecular Medicine. But in 2009, he came back to Singapore and gave up his tenured position at the University of Dundee. He explained in a 2009 The Straits Times interview that “there is a real opportunity to do something for cancer here”.
Sir David stepped down as CEO of ETC in 2009, which he said was the right decision. “I get things going but when it gets down to the details, keeping it going is less interesting to me. Besides, we were able to recruit Alex Matter, an outstanding drug discovery expert to take over from me.” He added, “Philip [Yeo], referring to my personality, said to me that I’m more a father than a mother.” He then moved on to become the chief scientist at A*STAR, a position he still holds. As chief scientist, he runs his own lab—named p53—and mentors young scientists. He also plays a research coordination role, and works with the directors of the different A*STAR institutes. He believes that it is important to “create a culture of excellence and self-criticism” and tells his staff not to rely only on approvals from journals as the litmus test for doing good science. Getting papers into a top journal does not mean that the results are immune from erroneous methodology and sloppy data management. In a recent case, a young Japanese scientist made a startling stem cell discovery that was published in Nature, the top science journal. Shortl
y after, she was found guilty of scientific misconduct. He thus makes sure that the methodologies his students use in their papers can be reproduced in the laboratory by two different people. Understanding the need for “face” in Asian culture, he does this tactfully. “When someone finds something interesting, then we should test it in another way, which someone else should try so that we don’t make mistakes and publish results that cannot be reproduced.”
Sir David recalled that when he arrived in 2002, then-Chairman of A*STAR Philip Yeo took him to the top of a building at Raffles Place and asked what he saw below. Sir David replied, “People” and Yeo said, “That’s it”. Sir David said he was slightly bewildered, and asked Yeo what he meant. Yeo continued, “That’s all we’ve got—people.” Sir David said the exchange impressed upon him an important fact: Singapore’s only resource is its people and so developing its human capital is key. It is also something that he believes in. Hence, when it comes to mentoring students, Sir David insists on teaching them teamwork. “You’ve got to succeed as a team and not as an individual,” he said. He encourages his students to collaborate and exchange ideas with one another, and to question one another’s view as well. The age-old archetype of a genius scientist competing with everyone else to publish a ground-breaking paper is a “terrible model”. He learnt that from Prof Mitchison at University College London. Calling him an eccentric scientist who was “tough but very good”, Sir David remembers his generosity fondly. This quality is one of the yardsticks he uses when hiring young scientists to work with him at A*STAR. “Generosity cannot be underestimated. If you’re generous to other people, they will be generous to you,” he said.