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The Virus Hunters: Singapore Researchers Part Of A Global Force Against SARS
Date: 25-April-2003
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While Severe Acute Respiratory Syndrome (SARS) wreaks health and economic havoc throughout the Asian region, scientists in Singapore, in collaboration with global experts, are racing to develop ways to diagnose and treat it before it takes an even bigger toll.
Thanks to cutting-edge gene hunting tools and a remarkable level of scientific cooperation, researchers appear to be closing in on the culprit microbe.
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In Singapore, Tan Tock Seng Hospital (TTSH) clinicians have collected samples from an infected patient, from which the virus has been cultured in the virology labs of the Singapore General Hospital (SGH). Researchers from SGH, Defence Medical Research Institute (DMRI) and Defence Science Organisation (DSO) worked together to isolate the genetic material of the virus. Using the same high throughput technologies that enabled sequencing of the human genome, scientists at Genome Institute of Singapore (GIS) have recently decoded the sequence of the viral gene - all this in just a matter of weeks".
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"The SARS work we are doing at GIS, in collaboration with several hospitals and clinical research groups within Singapore, is driven by a strong sense of mission," says Dr. Edison Liu, Executive Director of Genome Institute of Singapore. "This public health issue has an impact on all of us living and working in Singapore and has motivated us to devote our energies to this disease."
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Singapore is the fourth country to decipher the complete genome of the coronavirus, now confirmed as the cause of SARS. The research team at GIS has sequenced viral genome isolated from a SARS patient who contracted the virus directly from one of the first patients.
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Researchers in Canada, USA and Hong Kong have independently sequenced the viral genome.
"We have been able to work at this exceptional rate and sequence the gene in just three weeks because of the tremendous sharing of information, and quick access to pure viral samples," said Associate Professor Ren Ee Chee, Deputy Director of Genome Institute of Singapore.
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"Our first sequence, which will act a road-map, is just the start," he said. Further sequences at GIS will be completed in less than a day, and the institute has plans to sequence many more viral samples taken from different patients in Singapore.
"It is important to get several sequences, locally, and internationally - they will help scientists learn a number of things," said Prof Ren.
For one, deciphering multiple sequences will allow researchers to strengthen each others findings.
They will also allow scientists to trace strain differences or mutations that might occur. This is particularly important because coronaviruses are known to morph often, and there is concern that the virus has already begun mutating during its travel.
Lastly, and most importantly for human health, understanding the virus' genome is expected to improve the quality of diagnostic tests and eventually might lead to the development of a vaccine for the disease.
"To design a robust diagnostic, we need to capture all the common regions of the virus, across different isolates, in different continents - we don't want to miss any of them out," he cautioned.
The immediate goal of the 35 scientists working on sequencing, bioinformatics, virology and epidemiology of this virus, is to develop an effective test for SARS, using specific viral DNA fragments to prime PCR reactions.
"We have a specialised diagnostic test that targets the gene for RNA polymerase - a protein that is vital to virus reproduction," said Prof Ren. He stressed the need for this diagnostic to be improved constantly before it attains the required level of sensitivity.
The GIS team has designed some promising primers for this gene target, which they are now comparing with other research teams that are working on RNA polymerase.
The test, which is being thoroughly evaluated before being used at hospitals and other research institutions, will not be used as a mass screening kit on the general population. Instead, it will act as a tool to augment current screening methods of noting symptoms, carrying out chest x-rays to look for abnormalities and tracing contact history.
An important consideration with the test is that we don't yet know all the dynamics of the virus and whether the test is sensitive enough to pick up the virus all the time. The other worry is that the infection may have an early stage when the virus isn't detected by the test. The test is expected to be a work in progress, in part because this information is so new and needs confirmation, but also because as more is discovered about the nature of the virus and its behaviour in the course of infection, the tools to detect it will have to follow in parallel.
"What we have is Version One, and we are working on an improved Version Two which will be highly sensitive and specific in its detection of the virus. Such test reagents can assist in the diagnosis of SARS patients, but cannot be used for mass screening until it has been evaluated extensively," explained Prof. Ren.
Looking ahead, the institute stands firm on its commitment to help fight this outbreak by unlocking the secrets of this virus' genes. Scientists at GIS are scrambling to understand the exact genetic shift that took place to turn this innocuous virus into such a rogue; they are studying the viral blueprint to understand if animal-linked genes are involved. They hope that by understanding the proteins involved in the viral life cycle, they will help identify ideal targets for quicker, accurate diagnostics and life-saving therapeutics.
"We have a social and national obligation to pitch in for as long as the problem persists," said Prof Ren.
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