Some top scientists said they are moving rapidly on a number of fronts to jump-start treatment and prevention research, particularly on vaccines.

Experience with related diseases suggests a vaccine against the disease, caused by a newly found virus, may be possible. Development of drugs to battle the disease began shortly after the SARS pathogen was identified.

But they warn that, despite the urgent need for effective treatment and the fairly rapid progress in research so far, too many puzzles about the disease still have to be solved.

"This work cannot be done in a short period of time," said Jin Qi, director of the State Laboratory of Viral Genetic Engineering. "Although the speed of discovering the pathogen of the disease is stunning, there is still a long way to go to get the medicine or vaccines."

Scientists identified the pathogen of SARS as a new coronavirus only weeks after the World Health Organization (WHO) initiated a research collaboration involving scientists from around the world on SARS. This was rapid progress compared with the two years taken to discover HIV that causes AIDS.

With the causative agent of the disease identified, scientists have turned to the study of its structure and function, as well as the mechanism of the disease.

"We still don't know exactly at the moment how the virus causes the disease, how it is transmitted and why it has caused different syndromes in different regions," Jin said. "This is a totally new coronavirus which we have never seen before."

He admitted such unknown factors would in a way undermine the development of reliable diagnostic measures as well as drugs and vaccines.

But public calls for effective drugs or vaccines have grown even louder as SARS cases and the ensuing fatalities throughout the country rise daily.

Reliable diagnostic tool?

Chinese scientists have made headway in developing diagnostic tools for the disease along with their international colleagues.

Researchers from the Beijing-based Academy of Military Medicine were among the first in the world to develop diagnostic measures against SARS.

A team led by Professor Zhu Qingyu from the academy isolated the SARS virus on March 21 from four specimens they collected from SARS victims in Guangdong Province, weeks before the confirmation of the virus by the WHO.

They soon began developing a reagent to test for the virus in collaboration with the Beijing Genomics Institute (BGI), one of China's top genetic research centers. By the middle of April, they have developed a tool kit called enzyme-linked immunosorbent assay, or ELISA, which was approved for clinical application a week ago after undergoing strict review by relevant central government bodies.

The tool kit utilizes specially processed proteins isolated from the coronavirus to detect the antibody existing in the serum of SARS patients.

The first batch of ELISA has been applied in clinical diagnosis, according to researchers from the BGI.

Yet ELISA, while being a quick diagnosis, normally within hours, remains an ancillary measure, as it cannot be applied to patients until they have developed some SARS symptoms. Statistics from the BGI suggests a diagnostic accuracy of 96 percent on SARS patients 10 days after they fall ill.

The diagnostic process is further compounded by the fact that there often exists an incubation period -- an average of 2 to 7 days -- before the disease actually strikes. This makes early diagnosis, which has proved the key to save the lives of SARS patients, very difficult.

Meanwhile, technical defects in the diagnosis and poor understanding of the mechanism of the disease so far may increase the likelihood of the so-called "false negativeness." That is, those who appear to be healthy may eventually turn out to have SARS.

Other diagnostic measures which are likely to be quicker and more accurate have also been proposed and developed by various laboratories.

Pei Gang, president of the Academy of Life Sciences in Shanghai, revealed they are now in the process of developing diagnostic tools that work by detecting the SARS virus itself, rather than the antibody as in the case of ELISA, in the serum of the suspected patients.

"We don't have to wait till the antibodies of SARS virus appear in the serum to confirm the case," he said, adding that the test will be inexpensive and available at ordinary hospitals, compared to a similar test tool called PCR testing.

Jin also said that any diagnostic tools, no matter how urgent in need, should be quick, accurate and cheap to be applied clinically. Before that can be achieved, clinical observation remains the primary diagnostic means, he added.

Vaccine or drug

The call for vaccines emerged almost the same time the SARS virus was identified.

Various laboratories across the country are pursuing different approaches to making a vaccine.

It is still not certain that any approach will work, although several laboratories have declared vaccines will be available as soon as in a few months. And the SARS virus, which has been found to mutate rapidly, could outwit researchers' best efforts.

Vaccines are essentially killed or weakened viruses, or part of it, that persuades the immune system to attack an incoming germ before it can cause illness.

One of the most popular approaches is that employed in the preparation of polio vaccines 50 years ago. That is simply to grow cells in flasks, allow the virus to infect the cells and reproduce, and then kill the virus. The virus would then be injected as a vaccine, and although dead, it might retain enough characteristics to elicit an immune response that would later be effective against live SARS.

Yuan Zhenghong, director of the Shanghai-based Lab of Molecular Virology under the Ministry of Health, said they are taking this approach to develop SARS vaccine in collaboration with scientists from Hong Kong and Guangdong.

"This approach takes less time than those using genetic engineering," he said, adding that the vaccine may be ready in a few months if things go smoothly.

But risks exist that live viruses may go through the quality control system and cause disease.

A second vaccine approach involves deliberately using a live strain of the virus, but one so weakened that it is unlikely to cause disease.

Such a vaccine can generate a strong immune response, but it also poses risks. A chief one is that the weakened virus can mutate in a way that makes it virulent again, and the vaccine itself could set off an epidemic.

With the conventional approaches adopted by various labs, a new approach using genetic engineering has also been tried to make copies of a protein on the surface of the SARS virus.

The protein will be given as a vaccine, in the hope that the body will mount an immune response to the protein that would kick in again if SARS viruses bearing similar proteins came along later. But its effects have also been found to be unstable.

Despite the optimistic views some scientists hold that vaccines may be developed in a few months, many others are skeptical.

Jin cautioned that many more tests have to be done to rule out the human safety concerns even after the vaccine has been created in the laboratory.

"You have to go through the tests for its toxicity and effect, the first, second and third stages of clinical tests," Jin said. "It may take as long as two to five years."

In addition to the approaches to a vaccine, many other laboratories are engaged in developing drugs against SARS.

A US company called AVI BioPharma Inc. announced late last month it has designed a compound which it says may be capable of recognizing, locking onto and blocking replication of the virus.

Drugs like this are known as antisense compounds, which scientists say represent the most cutting-edge technology in the pharmaceutical industry and, if successful, may greatly speed up the development of new drugs, which normally takes over 10 years and costs hundreds of millions of dollars.

Chen Kaixian, director of the Institute of Pharmaceutical Research in Shanghai, said they have introduced the approach into their development of SARS drugs, while screening their library of chemical compounds they have already developed to see if any is active against the SARS virus.

Chen Wei, a researcher from the Academy of Military Medicine, said the anitsense drug theory has been in place for some time and proved useful in developing new drugs, but their clinical effect remains to be tested.

Jin was of the opinion that focus should be placed on the vaccines rather than drugs in the near future, as eradicating the virus from the host cells in the human body in which they reproduce has proved extremely difficult if not impossible.

"You cannot kill the virus and the host cells together," he said. "Vaccine should play a major role in containing the epidemic."

(China Daily May 9, 2003)