Scientists have identified the Sars virus and the symptoms can be treated. But will there be a pandemic, asks Science Editor Roger Highfield

Forget al-Qa’eda. Forget the military boffin who sold out to terrorists, or that rogue state intent on obtaining weapons of mass destruction. If the experience of Sars teaches us anything, it is that Mother Nature is the ultimate bioterrorist.

She can spring nasty surprises. An old agent can infect a new host - people - or a new human agent can emerge by mutation, or by blending its genes with sister organisms. This time, the result is Severe Acute Respiratory Syndrome, a novel pneumonia thought to have originated in the Guangdong province of China, which has now been spread worldwide by air travel.

What are the symptoms of Sars? Fever, dry cough, shortness of breath, headache and low blood oxygen.

What is the cause? The culprit appears to be a new virus from the coronavirus family. It has been found with astounding speed, given that the disease was only formally recognised at the end of February.

What is a coronavirus? One of the 200 or so viruses that cause colds in people. There are more than a dozen members of the coronavirus family that infect not only man but also cattle, pigs, rodents, cats, dogs and birds, according to Prof Ian Jones, a virologist at Reading University.

Gaze at coronaviruses under the microscope and you can appreciate how they get their name, appearing as an irregular sphere with a "crown" of spikes. Like any virus, they consist of a sliver of genetic material wrapped in a protein overcoat. In this case, the overcoat is spiked with fingerlike proteins which it uses to invade host cells. They are typically transmitted between people by aerosols when we sneeze, human waste, or by touch. About 10 per cent of Sars patients develop diarrhoea, suggesting that people can become infected by contaminated food and water.

The coronaviruses we are usually exposed to cause a mild, self-limiting disease (a typical "cold"). But Sars is different. For one thing, the virus grows in Vero cells (a primate cell line) - a novel property for coronaviruses, most of which don’t grow so easily. For another, the disease can be fatal in about five per cent of cases, usually when a person has been weakened by an underlying condition such as diabetes, heart disease or a depleted immune system. This falls far short of the 30 per cent mortality rate of smallpox.

Why are we sure Sars is caused by a coronavirus? For an agent to be blamed for a disease, it must fulfil Koch’s postulates: it must be in affected people and be isolated; and it should be shown to be capable of causing the disease. Conclusive evidence of the latter has come from monkey experiments, according to Dr Klaus Stohr, director of the World Health Organisation’s Sars investigation.

Conducted by Prof Albert Osterhaus at Erasmus University, Rotterdam, the monkeys developed a similar respiratory illness after the virus was introduced in their nostrils. Some developed pneumonia and an examination of their lungs revealed a similar picture to that seen in patients. The Dutch scientists also used a genetic amplification technique, RT-PCR, to reveal how coronavirus RNA had spread to the lungs, blood and faeces.

How did Sars evolve? Viruses pirate the cellular machinery of their host to mass-produce more viruses. Unfortunately for us, coronaviruses are "written" in a primitive genetic code, RNA, so they mutate more easily.

To carry out its instructions, RNA must be decoded by an enzyme called polymerase. This is a notoriously poor RNA "speller," causing mutations. Coronaviruses are among the biggest of the RNA viruses and, as a result of these mutations, their recipes vary greatly. However, there is a hard core of unchanging genes, those that are crucial for the virus to work properly. If they are found, there will be new opportunities to develop vaccines and treatments.

How do we know the virus is new? The sequence of letters that spells out the genetic recipe has been read by scientists in Canada, the US and the Far East. The sequence has almost 30,000 letters, compared with other members of this viral family, which range between 29,000 and 31,000 letters.Although the coronavirus is more than 75 per cent identical to known animal and human viruses in some regions, it diverges widely in others. This adds to the suspicion that this coronavirus is the cause of Sars, since people lack immunity to a novel virus.

The unusual sequence suggests that the coronavirus lurked undiscovered in animals before making the leap into humans, perhaps when people came into contact with infected animals to which they had rarely been exposed before. Or perhaps two strains met in an animal and swapped genes, as has happened with flu. Pigs are thought to act as "genetic mixing vessels" for human and avian flu viruses, and it is due to the proximity of people and animals that flu epidemics are born in the Far East, says Professor Jones.

Sars appears to be a mix of a mouse and a bird coronavirus, but this "recombination" event probably occurred long ago and was not the reason that it jumped to humans, says Professor Michael Lai of the University of Southern California, Los Angeles. "However, the fact that it is not similar to any known coronaviruses isolated from domestic animals [so far, this list includes pig, dog, cat, rabbit, mouse, rat, turkey and chicken] suggests that the Sars virus is most likely derived from a wild animal that came in contact with human beings recently. Probably, minor mutations allowed it to jump species."

Scientists plan to trace the origins of Sars by gathering samples from animals in Guangdong Province, where the disease probably arose, and hunting down "patient zero", who first developed Sars. They could also assess whether changing patterns of animal movement or agriculture might have aided the species jump.

What else can we do with the virus’s genetic sequence? Laboratories can use this information to develop tests, which will not take long, and to begin to assess antiviral drugs and develop vaccines, which will take time.

It will also take some time to work out why the virus is so nasty, says Professor Lai. "The sequence information suggests that this virus may contain a few genes seemingly unnecessary for its own replication or survival. These may be important for causing the disease. It reminds us of the Aids virus, which also contains more genes than the other common comparable viruses (retroviruses)."

Can we treat Sars? Yes, according to Prof Peter Hawkey of the University of Birmingham, who has been helping to treat patients in Guangzhou, where the first major outbreak of Sars affected 350 people. The patient must be quickly given "heroic" doses of steroids, which damp down the body’s response to the virus. "The virus does not kill you. It is your own inflammatory response, triggered by the presence of the virus of the lung, which damages the lung irreversibly in some patients; those that die," he says.

Will Sars cause a pandemic? Probably not, believes Prof Hawkey. "My own feeling is that we could well, if we are not careful, see a series of Toronto-like episodes. Local authorities must be vigilant." If newly infected Sars patients infect, on average, fewer than one person each, fewer and fewer people will be infected with each round of infection. If this basic reproductive number is less than one, an outbreak cannot sustain itself and will fizzle out. If the number exceeds one, however, the disease will affect ever-increasing numbers.

This, in turn, depends on various factors: how many times a Sars-infected person comes into contact with others; how likely it is to be transmitted each time; how long the disease incubates before symptoms - and infectivity - appear; for how long a case actually sheds the virus and is infectious. At Imperial College, London, Prof Neil Ferguson, Prof Roy Anderson and Dr Steven Riley are gathering information on the Hong Kong outbreak to model the spread of the disease internationally. "The question we and lots of others are trying to answer is what the potential is for this to turn into a global pandemic," says Prof Ferguson. "We can’t answer that at the moment."
(C) The Telegraph Group London 2003