LURKING THREAT? SARS has subsided for now, but it could make a comeback. The image above shows coronavirus isolated from a SARS patient. Image: ARMED FORCES INSITUTE OF TECHNOLOGY Contributed by Charles Humphrey and Anthony Sanchez of the National Centers for Disease Control and Prevention
The global SARS panic has fizzled. In early July, the World Health Organization (WHO) deemed all known chains of person-to-person transmission broken and cautiously pronounced humans SARS-free. Quarantine and isolation seem to have snuffed out the flames for now. But where SARS still smolders is not known. As world health officials draft priorities for the long-term response to the new disease, evolutionary biologists warn against embarking on vaccine development without a fuller understanding of where the virus lurks and how many genetic variations it has. To do so, they fear, could lead health experts down an unnecessarily long and cumbersome trail to treatment and prevention¿or worse, to a more virulent form of the disease.
The first line of defense against emerging infectious disease is epidemiologists. They grapple with questions ranging from how long the virus incubates before transmitting to a new host to how many new cases come from each sick person. After their detective work is complete and the virus has been traced back to its origin, evolutionary biologists tackle what the virus is doing and how genetic changes affect its ability to infect humans. The questions they seek to answer push the limits of science: Not only do they probe how a particular virus came to harass humans in the first place, they also look to predict how it will change as it adapts to our species. But some evolutionary biologists complain that their know-how is underutilized, pointing to the abysmal failure of vaccines against HIV¿the virus responsible for AIDS¿and flattened hopes for a drug cure as an example of infectious disease management gone wrong, because of poor data on the evolution and genetic diversity of the virus.
At the first global conference on SARS held in Kuala Lumpur, Malaysia, in mid-June, the top two priorities set by the WHO were the development of an effective measure to stop SARS transmission¿ideally a vaccine¿and an inexpensive, easy-to-use diagnostic test. According to a June 18 WHO report, experts agreed that not enough is understood about the origins of the new virus. Failure to specifically address the ongoing evolution in the relationship between SARS and its new human host has some evolutionary biologists worrying that the rush for a cure could follow the same ill-fated path as the quest for a quick fix for HIV.
In recent years, international organizations and governments have begun to channel funds into understanding the full panoply of HIV variants on the loose in the population. But for decades, most of the money was spent searching for a drug cure for the disease. Subsequent efforts to develop a vaccine have borne no fruit; the most recent disappointment coming from the much anticipated VaxGen clinical trials, in which the company¿s HIV vaccine, AIDSVAX, did not lead to a statistically significant reduction in HIV infection. The study revealed the ignorance of the medical community to the high degree of variation in the HIV virus within the U.S., says Keith Crandall of Brigham Young University, a consultant on the VaxGen study.
"Failure to monitor how viruses are adapting to human hosts will continue to allow viral evolution to proceed haphazardly, favoring harmful strains in one setting and mild strains in another," comments Paul Ewald of the University of Louisville. Like HIV, the SARS virus contains only a single strand of RNA, and lacks the "zipper" feature seen in its double-stranded cousin, DNA, that ensures more accurate replication. Left to its own devices, RNA makes mistakes as it copies itself and thus mutates rapidly. When developing vaccines, scientists often use a live but benign strain of the virus. The strain used must be similar enough to the disease-causing forms to allow the immune system to build up defenses against the virulent variety but not so similar that it causes disease or could easily evolve virulence. For a rapidly mutating RNA virus, as SARS is believed to be, such a strategy would be difficult at best and doomed to fail without a clear picture of how a strain selected for a potential vaccine stacks up, not only in terms of the number of mutations from the generic strains but also in terms of the molecular function of those mutations.