SARS  pg. 7

Denison argues that all of the various vaccine strategies must be pursued because we don’t know how studies of animal viruses will translate to human beings. “Other investigators and I agree that inactivated virus strategies are likely the safest and may work,” he says. “But they haven’t worked anywhere else (in animal studies), so it’s not wise to only pursue that approach—you’d put yourself way behind the curve.”

Using a genetic system they developed for modifying the mouse hepatitis virus, Denison and colleagues plan to introduce mutations into the SARS coronavirus genome and assess the effects of these mutations on the ability of the virus to infect cells, reproduce and cause disease. Their goal is to create viruses that grow well in culture but do not cause disease, and which could be candidates for a vaccine. They’ve had success with this approach using the mouse hepatitis virus as a model.

If inactivated viruses turn out to be a viable strategy for vaccinating humans against the SARS coronavirus, Denison says their technique for modifying the viral genome would likely still be useful for safely growing the large quantities of virus needed to produce the vaccine. By January 2004, China was already moving to human studies of an inactivated virus vaccine, a government official announced.

Denison smiles about the wealth of resources now being devoted to coronavirus research; it makes his scientific life easier, after all. But he hasn’t forgotten his days in the trenches studying a virus no one thinks about.

“What this outbreak taught us was not just about coronaviruses,” he says. “We need to understand the capacity of all kinds of viruses to move between species and the mechanisms by which they cause disease. We need to make sure that there are fundamental things that we know about all identified viruses—their genomic sequences, for example, and some basics about their biology.”

Now that influenza has claimed the headlines, Denison says his daughter Julia wonders why he’s not working on the flu virus instead. “I think she reflects the general attention span of the public for newly emerging viruses,” he says. “But I live in this world because I understand that if we’re successful—if we prevent disease through vaccination and other public health measures—people will say, ‘What was the big deal?’”

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