Not Born in Singapore

by Tng Ying Hui

  References

  A*STAR, 2009. Professor Sir David and Professor Birgit Lane to resume full-time Appointments at A*STAR From September 2009.

  Nikolai Zhelev, “Man of Science: Celebrating Professor Sir David Lane’s 60th anniversary,” Biodiscovery 1 (2012).

  Interview with Sir David Lane in April 2015.

  Sir David Lane

  United Kingdom, b.1952

  Dr Edison Liu

  The SARS Detective

  Hong Kong-born cancer researcher Edison Liu played a vital role in the battle against SARS and laid the foundations of genomic research in Singapore.

  In March 2003, Singapore was struck by a medical crisis—the arrival of the Severe Acute Respiratory Syndrome (SARS), a highly contagious form of pneumonia. Faced with a deadly disease that could be easily mistaken for the flu, Dr Edison Liu led his group of scientists to unmask the killer.

  Within six weeks the team developed a test kit that could accurately identify the SARS virus and distinguish it from other, more benign viruses. Only a small amount of serum, plasma or blood was needed from the patient.

  Developing the kit was the easy part, said Dr Liu, the first executive director of the Genome Institute of Singapore (GIS). “What was complicated was the integration of all the components of the healthcare system so they would work smoothly together with the researchers,” he recalled.

  The team was also battling against time. “People were dying in Singapore and the nation was brought to a standstill. We had to act,” he said. Indeed, the period between March and May 2003 was gloomy for Singapore. Schools were shut, everyone went around with masks, hundreds of people were home-quarantined and healthcare workers who had cared for SARS patients fell to the disease. The tourism sector in Singapore and other Southeast Asian economies were hit hard as hotel occupancy rates, tourist arrivals and retail sales fell dramatically.

  Dr Liu, a graduate of Stanford University, had wanted to be a doctor since he was a child. Today, he is feted by the world's leading scientific institutes for his work in cancer research and genomics. He received the Public Service Medal in 2003 for his contribution to combating SARS.

  Dr Liu came to Singapore in 2001, leaving a high-powered career at the National Cancer Institute in the United States where he managed 1,200 people, for a country whose biomedical industry was still in its infancy. At the time, Singapore’s Biopolis had yet to be built.

  But Dr Liu, whose earliest impressions of Singapore were shaped by British writer Somerset Maugham’s whimsical tales of Southeast Asia, believed that the island-nation had enormous potential to be a biomedical science hub in Southeast Asia. Singapore, he said, had been at the centre of the Asian miracle. “I wanted to have the opportunity to create something from nothing,” he said, when describing his interest in building a renowned genomic centre in Singapore.

  In an interview with The Straits Times in 2006, he praised the country's attitude to research funding, saying, “Singapore now has a pipeline that runs from the basic fundamental scientists all the way to the point of care.” On top of that, directors at the different R&D institutes are given the freedom to execute their vision, he said.

  At the GIS, the two-term president of the Human Genome Organisation focused on transcriptional regulation. In 2001, as scientists dashed to complete the human genome, the next most pressing question was how to understand the orchestrated functions of genes.

  Here, Dr Liu integrated population studies with the analysis of genomic changes and mutations to uncover their control of human cancers. The genome is a complete set of DNA in an organism. Singapore’s three major racial groups—Chinese, Indian and Malay—provided a convenient gene pool for his work, he noted, which was further aided by “well-kept clinical databases”.

  He developed a five-pronged strategy to put Singapore on the genomics world map and show that a small country could compete with large ones in the field. His plan was: First, study genomics in the medical context. Second, develop a robust R&D infrastructure. Third, provide rigorous training in genomics sciences. Fourth, partner academic institutes with complementary skills and needs. Fifth, encourage the life sciences industry to become one of the island's economic drivers. His strategy paid off, Dr Liu said, and the GIS is regarded as one of the best in the world today.

  Research papers by GIS staff are published in top-tier journals, such as Nature, Science, and Cell, and its scientists are highly sought after. GIS is one of three foreign institutions whose scientists have been invited to join the exclusive US-based ENCyclopedia of DNA Elements (ENCODE), a global collaboration on the human genome.

  Getting to that stage took some doing. One early hurdle was convincing top scientists to give up their established careers for an untested biomedical industry in Singapore. Dr Liu thus recruited promising young scientists, whom he described as “diamonds in the rough” with “hunger in their eyes”.

  He also had to forge a middle ground by reconciling the expectations of government funding agencies with the realities of science. “Anything that generates expected data is usually not interesting and certainly not ground-breaking,” he explained, adding that the discoveries in genomics that have meaning and impact come only after deep analysis of complex data sparked by radical thinking.

  There were administrators who considered his approach feckless. Critics asked him when they would see tangible outcomes from the amount pumped into life sciences research. Dr Liu would first respond, “When will you see the rate of return on primary school education?” before explaining that the life sciences had a unique life cycle. Research, he said, is a long-term investment that requires a certain amount of risk-taking, and money poured into it will not see returns until later on—when that research is eventually applied in real life.

  In 2003, at the official opening of the Biopolis, Dr Liu, a competent jazz pianist, played a number that he had composed himself. It was titled “Yeo Bro”, a tribute to then-Trade and Industry Minister George Yeo and then-Chairman of A*STAR, Philip Yeo. Both of them had been deeply involved in Singapore’s life sciences push.

  Today, the life sciences industry faces another challenge—the allure of China. As foreign companies rush there to establish R&D units, Singapore needs to adjust its strategy, said Dr Liu. To stay competitive, it is important for Singapore to attract global talent, and to recognise and support its own talent.

  The Hong Kong-born researcher and American citizen became a Singapore Permanent Resident in 2008. But in 2011, he returned to the US to head the Jackson Laboratory, a biomedical research institution, where the aim is to lead the worldwide search in the cure for cancer. He often performs jazz piano for local functions in Bar Harbor, Maine, where he is currently based. For the first one and a half years, Dr Liu came back about three times a year to complete his research. These days, he is back once or twice a year for seminars, collaborations and to meet up with friends.

  Looking back, one of his proudest moments was the choice of a Singaporean, Dr Ng Huck Hui, to succeed him: “His appointment was a signal that Singapore is ready to lead its own bioscience efforts. My job was done.”

  References

  Amy Tan, “Singapore to Delve into Human Genetic Code,” Reuters, March 21, 2001.

  “Cancer Expert to Head Genomics Programme,” The Business Times, January 31, 2001.

  Mia Shanley, “Singapore’s Biotech Pipeline Show Promise,” The Straits Times, April 11, 2006.

  “Music in Their Genes- or Other Way Round?” The Straits Times, October 30, 2003.

  “Singapore Biotech Drive Loses Star UK Scientists,” Reuters, September 20, 2007.

  Interview with Dr Edison Liu over Skype in December 2014.

  Dr Edison Liu

  Hong Kong, b.1952

  Sir George Radda

  An MRI Pioneer

  An expert in magnetic resonance imaging, Hungary-born Sir George Radda has helped build up Singapore’s bioimaging capabilities since 2003, when he first served as a member of A*STAR’s B
iomedical Sciences International Advisory Council.

  Magnetic resonance imaging (MRI) is a vital tool in medicine for diagnosing tumours and spotting injuries to muscles and ligaments. At the turn of the 21st century, Singapore’s hospitals possessed several bioimaging machines—which used technology to visualise biological processes in real time—for research. In 2005, Sir George Radda became the founding chairman of the newly-established Singapore Bioimaging Consortium (SBIC), which identified and consolidated the various bioimaging capabilities across research institutes, universities and hospitals. Its aim was to foster closer collaboration in bioimaging among researchers and medical practitioners.

  Sir George was born in Hungary in 1936. He grew up witnessing political change as Hungary went from being a monarchy to a communist republic, with the continued presence of Soviet military troops. In 1956, when there was a nationwide revolt against the government, he and his siblings fled to the Austrian border, with a few clothes and a little cash. Sir George bribed soldiers to let him and his family through. In Vienna, he met a group of academics from the University of Oxford who were searching for promising students among young refugees. Sir George impressed them so much that by mid-December 1956, he was accepted into Oxford. He went on to graduate with a First Class Honours in Chemistry and received his PhD in 1962. After a brief research stint in the United States, he became a lecturer at Oxford.

  Sir George has been involved in the field of medical imaging since 1969. He started out exploring the uses of nuclear magnetic resonance—which has since evolved to a more commonly known term, MRI—to study the operation of muscle tissues. His pioneering work led to the making of the first high-field MRI scanner—which produced very detailed pictures—that was large enough to accommodate a human body in 1983. Installed in a hospital in Oxford, United Kingdom, the scanner used MRI to monitor the inner workings of the human body. Today, MRIs are used by hospitals worldwide to spot lesions and tumours in human bodies. When the idea of setting up a biomedical science hub in Singapore was mooted in 2000, Sir George was courted by then-chairman of A*STAR, Philip Yeo, to be part of the country’s biomedical push. In 2002, he came to Singapore to give public lectures in schools and varsities. This gave him the opportunity to survey the calibre of students here. He was taken by surprise when junior college students waited in line to ask him questions after his speech. He was also amazed when the venue at the NUS where he was lecturing was packed with students from not only the science faculty but also various other faculties. Overall, he found the students in Singapore “very bright”.

  In 2003, Sir George was about to retire from the UK’s Medical Research Council, a government agency that directs all medical research in the country, after seven years at the helm. He was approached by Yeo to advise Singapore on its biomedical plans. Sir George agreed and served as a member of Singapore’s Biomedical Sciences International Advisory Council.

  At the 2004 Biomedical Research Council (BMRC) meeting, bioimaging was identified as a key area for development. Improvements to bioimaging technology would improve medical care, as images would be sharper and this would make it easier to spot lesions and tumours in human organs. This was seen as a worthwhile area of investment for Singapore. Sir George agreed, saying that “bioimaging is at the forefront of medical research”.

  Sir George was asked to start a bioimaging consortium. It was called a “consortium” because the development of imaging technologies meant bringing together experts from fields such as computer science and biology, from different research institutes in Singapore. In 2005, the SBIC was established and Sir George became its founding chairman. He remained its chairman until 2010. During those five years, he was also the head of the Department of Physiology, Anatomy and Genetics at the University of Oxford. He lived in the UK but travelled to Singapore every month.

  One of the challenges he encountered in Singapore, Sir George recalled, was finding an appropriate location to set up a bioimaging laboratory. The MRI machines were huge and they had to be kept away from metallic objects, so the lab could not be built below a carpark. The floors of the building also had to be strong enough to hold the machines’ weight. Today, the SBIC is located in the Helios building in Biopolis.

  Working together, SBIC and the NUS established the Clinical Imaging Research Centre (CIRC) in 2007. Using state-of-the-art bioimaging tools developed by Siemens, the CIRC is one of the few facilities in the world dedicated to doing clinical R&D in bioimaging. Under Sir George’s leadership, the CIRC has made advances in clinical R&D. In 2008, it installed a 3 Tesla scanner, which with its increased resolution from the scans, produced sharper pictures that would help healthcare providers to detect diseased organs earlier and treat cancer in its initial stages.

  Sir George, who was given the 2008 Public Service Medal and was conferred the Honorary Citizen Award in 2015 for his contributions to the development of research in Singapore, succeeded Sir David Lane as the chairman of the Biomedical Research Council (BMRC) in 2009. The BMRC coordinates the country's biomedical activities and oversees institutes in the Biopolis, a hub of more than 2,000 researchers and staff. “It is typical of the Singapore way—you do one job for them, they ask you to do two others,” he quipped.

  References

  Dr SJ Gurman, Professor Sir George Radda – Doctor of Science - Former Chief Executive of the Medical Research Council, accessed October 2015, http://www.le.ac.uk/ebulletin-archive/ebulletin/publications/2000-2009/2006/07/npfolder.2006-07-11.5678371783/raddaoration.html

  “Sir George Radda recognised with Academy’s most prestigious award,” CV Network,

  accessed September 2015, http://www.heartacademy.org/newsletter/4/4.pdf

  Singapore Bioimaging Consortium,. 2015, Announcements, https://www.a-star.edu.sg/Portals/16/Images/Announcements%20and%20Seminars/SBIC_Statement_%20Apr08.pdf

  Interviews with Sir George Radda over Skype in April and June 2015.

  Sir George Radda

  Hungary, b.1936

  Prof S. S. Ratnam

  Putting Singapore on the Medical Map

  Sri Lankan-born Prof S. S. Ratnam came to Singapore as a young medical doctor in the late 1950s. His groundbreaking work has since put Singapore on the medical map in more ways than one. While his work with transsexuals has won him media attention, he was also a leader in reproductive biology, helping couples have children.

  The terms “visionary”, “formidable figure”, “trend-spotter” and “pioneer” are commonly used to describe Professor Sittampalam Shanmugaratnam, also known as Prof S. S. Ratnam. Much of his work broke new ground. He was a leader in reproductive biology, giving Asia its first test-tube baby through in-vitro fertilisation (IVF). He and his team also provided many childless couples with hope, by devising other methods of having a baby—by implanting frozen embryos and through improving the reproductive capabilities of weak sperm, among others.

  Born in 1928, Prof Ratnam’s uncle, maternal grand-uncle and cousins were all doctors, and his mother wanted him to follow in their footsteps, so he attended medical school. In 1957, Prof Ratnam completed his studies at the University of Ceylon. He came to Singapore to do an internship at the Singapore General Hospital and in 1963, joined the University of Singapore’s Obstetrics and Gynaecology (O&G) department as a lecturer. In 1970, he became head of the O&G, retiring in 1995 at the age of 67. He worked tirelessly to train young doctors and saw the department through a series of firsts. He purchased its first ultrasound machine, and in 1971, he wrote medical history when he developed a series of surgical operations to transform the phenotypic sex or the physical genital characteristics defined within each sex. His interest in this field was sparked in 1969 when a Singaporean patient begged for a sex-change operation. At the time, the patient, who had been born a man, had attempted suicide twice. Prof Ratnam initially sent him to a psychiatrist, but the patient returned to his clinic every week, appealing to him to do the operation.

  Prof Ratnam, who was influenced by his mother’s stro
ng belief that one should help others, studied what had been written on the complex procedure and even practised doing it on cadavers in the mortuary before he agreed to operate on the patient. In 1971, he performed a successful operation and paved the way for sex-change surgery in Asia. He received many more requests, and doing his best not to decline too many, he worked 14-hour days—seeing patients, researching, writing papers and attending meetings. He did not take vacations or rest on weekends. In a 1996 interview with The Straits Times, he confessed, “I can’t bear the idea of not doing anything. I have to keep busy and asking questions. Otherwise, I have no business being in research.” During Prof Ratnam’s tenure at the O&G department, it was designated as one of 13 World Health Organisation Collaborating Centres for Research in Human Reproduction in 1972. This gave it worldwide recognition and international funding for its research projects.

  In 1981, Prof Ratnam received an award from the Association of Southeast Asian Nations for his contributions to reproductive medicine. In 1983, he led a medical team to successfully produce Asia’s first test tube baby. This came after an initial failure—he tried to carry out embryo replacement in 1982 at his lab for IVF in Singapore, but the procedure failed. He attempted it again a year later, applying what he had learnt from that first effort. This time, a healthy baby boy was born.

  In 1986, he became Asia’s first doctor to help a woman become pregnant using Gamete Intrafallopian Transfer (GIFT), a procedure whereby fertilisation happens naturally after eggs and sperm are placed directly inside one of the fallopian tubes. In 1987, he managed another first—conceiving a baby through IVF, using a frozen embryo. His patient had attempted twice to get pregnant through the usual IVF method—using a freshly fertilised embryo—but that had failed. On the third try, an embryo preserved from a previous cycle was implanted, a rare procedure then. In 1988, the Singapore Science Council conferred the National Science and Technology Award—the highest honour bestowed on outstanding scientists in Singapore—on Prof Ratnam.