It was February and a team of scientists from the University of Hong Kong had embarked on a fishing expedition, but this was no pleasure cruise. Their radar screen was on the alert for an elusive catch - a virus that Guangdong officials announced on February 10 had infected 305 people since November, killing five. It was a form of atypical pneumonia and the team, members of a Hospital Authority taskforce set up on February 11, was looking for similar Guangdong pneumonia cases in Hong Kong. Earlier that month, they thought they had netted the bug: a mutant flu. H5N1 flu (bird flu) had killed a 33-year-old man and infected his nine-year-old son, both of whom had visited Fujian province - the second time the flu had jumped the species barrier. In 1997, in Hong Kong, six people out of 18 infected had died from the disease. But there was no evidence of flu or any of the other known respiratory viruses that afflict humans. 'By the end of February, we began to believe that we may be looking at a new virus,' says epidemiologist Malik Peiris, chief of virology at HKU. 'We were thinking this might be something unusual.' The Hospital Authority taskforce, meanwhile, sent a report to the Hospital Authority Board on March 7, warning that the atypical pneumonia in Guangdong might be an 'unusual virus'. Days before, Queen Mary Hospital doctors led by Professor Yuen Kwok-yung were called in by Kwong Wah Hospital to treat Guangdong nephrologist Liu Jianlun, who was admitted on February 22. He had checked in at the Metropole Hotel in Mongkok a day earlier to attend a wedding. He would become known as 'patient zero'. His Hong Kong brother-in-law, who spent 10 hours with Liu shopping and sightseeing, was admitted to the same hospital on February 28. Both died. In hindsight, Professor Peiris said, at the time there was nothing to indicate that these patients were any different from many others suffering pneumonia in Hong Kong. Then on March 10, the Department of Health announced it was investigating reports of Prince of Wales Hospital staff falling ill with atypical pneumonia. It was clear that the Guangdong pneumonia had arrived in Hong Kong. Almost simultaneously, Vietnam, Singapore and Toronto reported similar cases after the World Health Organisation (WHO) was informed by Hong Kong about the Prince of Wales Hospital (PWH) outbreak. At the hospital, an airport worker who had visited the Metropole's ninth floor at the same time as Liu had been admitted to Ward 8B on March 5 with a fever, but no connection to atypical pneumonia was made. He had been treated with a nebuliser which had sprayed minute viral-laden mist on to nearby patients, hospital staff and medical students. By March 15, the WHO had named the severe form of pneumonia Sars - severe acute respiratory syndrome. A global alert was on, as 150 new cases were reported in eight countries. Declaring Sars as the first serious new disease of the 21st century, the WHO pulled together 13 laboratories - including HKU and the Chinese University of Hong Kong (CU) - in various countries, to identify the cause of Sars. On March 18, CU doctors led by its dean of medicine, Professor Sydney Chung Sheung-chee, and including professor of microbiology John Tam Siu-lun announced that through electron microscopy they had isolated a paramyxovirus, which causes measles and respiratory disease in babies, as the likely cause of Sars. But patients with the unusual pneumonia who had been studied by the HKU experts showed no evidence of paramyxovirus. The HKU team, meanwhile, continued with their research for the elusive virus, convinced it was more than a mutant paramyxovirus. 'In fact we did not only look at the flu,' says Leo Poon Lit-man, assistant professor at the HKU's department of microbiology. 'We also looked at other viruses which are known to cause respiratory disease, such as adenovirus, respiratory syncytial virus, influenza B, rhinovirus, paramyxovirus and human metapneumovirus - but in our hands none of them were positive,' Dr Poon says. The 10-man team then began to cast their net wider, using different approaches, molecular and genetic, 'to try to fish out the new virus', says Professor Peiris. The specimens from the brother-in-law and a female patient, two of four people tested after returning from Guangdong, were put through a range of new tests for new viruses. On one special cell line used to grow hepatitis rather than respiratory viruses, they began to see something. 'It was on one of these new cell lines that we saw the first clue,' says Professor Peiris. 'We had what looked like a respiratory virus.' His colleague, assistant professor in the department of microbiology, Chan Kwok-hung, was sure they had isolated the virus. Blood samples from the two patients taken during early and late stages of infection tested positive for the virus. The team discussed their results with Dr Wilina Lim, head of the Government Virus Unit in the Department of Health. 'We knew then that we had the virus causing Sars,' Professor Peiris says. At this point, the team used two approaches to identify the unknown virus: an electron microscope to visualise the virus and a special molecular technique to fish out pieces of unknown viral genetic material. Using a powerful electron microscope, Dr Lim and associate professor at the department of pathology John Nicholls saw that the virus size and appearance was suggestive of a group called coronaviruses. This was quite a surprise. Coronaviruses generally cause a mild disease in humans - the common cold. At the same time, Dr Poon's genetic fishing expedition with another colleague, Associate Professor Guan Yi, was also going well. 'Just like fishing, you catch something but you really do not know what fish it is until you pull the whole thing out,' he says. This time it was a big fish. It took Dr Poon four days of work, 15 hours a day, until he found one genetic fingerprint that bore a resemblance to a known family of viruses: the coronavirus. To fully sequence the gene, the HKU microbiology department called in its science department and seven of its postgraduate students for help. On April 16, nine days after they started the sequencing work, the team of enthusiastic students and their mentor, dean of science Professor Frederick Leung Chi-ching, announced they had fully coded the coronavirus genome. The sam had been achieved two days earlier by crack teams at the Genome Sciences Centre of the British Columbia Cancer Agency in Toronto and the Atlanta-based United States Centres for Disease Control and Prevention (CDC). The Chinese University's team led by its associate dean for medical research, chemical pathology professor, Dennis Lo Yuk-ming, uploaded on to the CU's website the complete sequence of the coronavirus in the PWH patients hours later on April 16. Many labs in the WHO network have since been using molecular tests provided by CDC to confirm the presence of a coronavirus in specimens from patients in various countries. The WHO upheld the HKU finding and announced that a novel coronavirus was the likely cause of Sars. 'The pace of Sars research has been astounding,' says David Heymann, executive director, WHO Communicable Diseases programmes. 'Because of an extraordinary collaboration among laboratories from countries around the world, we now know with certainty what causes Sars.' Until Sars surfaced, there were only 11 known animal coronaviruses. 'With this virus, all bets are off,' said one of the few coronavirus experts in the world, Arnold Monto, professor of epidemiology at the University of Michigan School of Public Health. 'It doesn't behave like the other coronaviruses.' Until Sars, it was thought that the coronavirus did not jump from one animal species to another. He said the coronavirus might have undergone a major genetic change when it jumped from animals to humans. Days later, the HKU's coronavirus was put to the test in Hong Kong. After developing a diagnostic test for the virus, the tool proved to be crucial for containing the spread at Amoy Gardens. Quick-test results established that the Sars virus was also being excreted in human waste, and that a kidney patient, mistakenly treated for flu at Prince of Wales Hospital's Ward 8A and released, was suffering from diarrhoea and discharged the virus when he used the toilet in his brother's flat in Unit 7 on the 12th floor of Block E in Amoy Gardens. A faulty sewerage system soon spread the virus in the 33-storey block from March 24, rapidly peaking three days later. During the outbreak at Amoy Gardens, these tests made the diagnosis of one of the causes possible within a day, Professor Peiris says. It had previously taken a week. The coronavirus was found in human waste and in wash basins and toilets in Block E. As for all viruses, there still is no effective Sars drug, and a vaccine is a long way off. The battle might have been won for now, but the war is not over. Experts say coronavirus strains are seasonal, dying off in spring and re-emerging in autumn. Chair Professor of paediatric surgery at HKU, Paul Tam Kwong-hang, who is also with the HKU Genome Research Centre, says the coronavirus research work was 'a fine example of a translation of genomic research into clinical application. Without proper genomic research we cannot fight disease, we cannot save lives.' Support from experts for a US-type Centre for Disease Control and Prevention to control Sars or other infectious diseases, and a dedicated infectious disease hospital, has been expressed. Hong Kong, they say, just cannot afford to relax.