Paul Turner of Yale University has studied how incorporating carefully calculated mutations that amplify the weaknesses of other mutations in a viral strain can best utilize researchers?understanding of evolutionary biology to prevent live vaccines from adapting to human hosts. Public health experts, he says, are not trained to understand the pitfalls of how a particular disease can change and how its relationship to the host can also morph over time. "What you¿re implementing today could be set up for failure only a few years from now," Turner warns. "The way you manage the disease could actually put more in favor of the pathogen changing to a more virulent form." Researchers could target only a subset of the gene pool and thus inadvertently hand unknown¿and potentially more lethal¿strains a selective advantage.
But hope is not lost, Turner asserts. He and others view SARS as an opportunity for evolutionary biologists to interact with public health officials to make great strides in combating the disease. "With recent outbreaks it¿s becoming more apparent that at least [public health experts are] thinking about evolution," Crandall says. An evolutionary tree showing the origin of the SARS virus even appeared in the May 30 issue of Science. Still, it wasn¿t up to snuff, he notes. "They¿re not using the information to its fullest advantage. They draw the tree and draw circles around different groups and say, ¿Look, here¿s our SARS virus and here are these other coronaviruses and somehow it must be related to these other things.? What they¿re missing, Crandall observes, is what each change in the genome means to the function of the virus.
For his part, Crandall is studying SARS from a bioinformatics standpoint, looking at variants of the disease and identifying those nucleotide sites that have mutated without affecting viral function and those that have conferred a selective advantage to the virus. This sort of analysis, he explains, is key to understanding how new forms arise and will enable scientists to think more creatively about combating those particular sites that dictate the disease-causing characteristics of SARS. "It lets you know where the important changes have happened to make this a distinct virus," he says. Drugs can then be developed to target the specific sites that have mutated to enable the virus to infect humans, or to create a vaccine based on specific regions of the genome that have clear and meaningful differences from other coronaviruses.
In a matter of weeks the global scientific community has sequenced and shared 21 strains of SARS on GenBank, the National Institutes of Health¿s Web-based database of genomic information. Considering the speed with which that was accomplished, evolutionary biologists believe a broader survey of the genetic diversity of SARS is feasible in the short term. At last count, the WHO reported 8,437 cases of SARS and 813 deaths. Crandall is inclined to believe that more than just the 21 known variants caused disease in those people. "If you took a month to collect 500 isolates and sent them off to genomics labs, they¿d crank them out and within a year¿it would take a while to analyze such an enormous amount of data¿you could expect to have a very nice picture of the global diversity of SARS," Crandall remarks.
If SARS does indeed turn out to be highly variable and it reestablishes itself in the human population, a full understanding of how different strains cause disease will be critical, Ewald says. He believes that provided diagnostic tests are developed, such knowledge will enable scientists to treat the disease selectively, in a way that focuses on preventing the transmission of the most disease-causing strains, thus steering the virus toward a more benign character. Even if our ability to treat the disease progresses no further than it is today, with a better grasp on what¿s out there we can still use quarantine and isolation to our fullest advantage.