Mining History to Fight the Flu
Chief of the Division of Molecular Pathology, Department of Cellular Pathology, Armed Forces Institute of Pathology, Washington, D.C.
“Definitely get your flu shot!”
The effort to decode the genes of the deadliest virus in human history got started because of chemist John Dalton’s 150-year-old eyeball.
The Armed Forces Institute of Pathology in Washington, D.C., has a unique collection of millions of tissue samples going back more than 100 years.
Jeffery Taubenberger and his colleagues at the Institute had developed unique methods to analyze the molecular make-up of preserved tissues. They used the methods to look for the genetic mutation
for colorblindness in a snippet of the venerable chemist’s preserved ocular tissue. Then they began to ponder what other uses they could put the technique to.
“The 1918 flu was by far and away the most interesting thing we could think of because it’s not just a historical curiosity, like John Dalton’s colorblindness," says Taubenberger. The 1918 pandemic
was "the most lethal infectious disease outbreak probably in all history and no one was able to study it because the virus wasn’t isolated at the time — influenza viruses weren’t even known to exist in 1918," he adds.
Some 525 million people were infected by the so-called "Spanish flu" virus, with more than 20 million people dying during the pandemic from 1918–1919. By comparison, approximately 60 million people have been infected with HIV since the start of the global epidemic in 1981.
|Influenza virus courtesy of the Centers for Disease Control and Prevention.
Since flu viruses are constantly mutating and other pandemics are anticipated, "it seemed to us that it would be useful to know something about the worst one and use that as a model to study how influenza viruses do what they do,’’ says Taubenberger.
“We’re not going to find a so-called smoking gun, a specific change in the genetic structure of the virus. I think what we have is probably a lot of subtle changes in all the genes of the virus that made this virus very fit and that are going to be difficult to dissect from one another.” Scientists know that the 1918 virus had novel surface proteins
, leading them to infer that people under age 40 probably had not developed any kind of cross-protective immunity to this new virus through previous exposure to earlier, similar flu viruses.
Moreover, historical factors also likely played a role. The global war entailed massive movements of people long distances, and crowded conditions in troop ships and barracks; these factors were ideal for spreading a contagious respiratory virus.
Nonetheless, Taubenberger and his team hope to learn enough from the 1918 viral genome to help devise or improve systems for predicting future pandemics. “Predicting a pandemic is difficult because we don’t really know how pandemic strains occur,” Taubenberger says. “It could be there’s no one universal model.”
In the meantime, Taubenberger believes surveillance of flu viruses should be enhanced to include scrutiny of flu strains in animals as well as those in people. After all, flu viruses infect birds and pigs, too.
“The current surveillance system isn’t looking for exposure to flu viruses adapted
for life in birds or other animals. It’s probably necessary to look at how these flu viruses get from animals to humans and how often this is occurring. Are exposures at low levels occurring all the time in people who work with animals? The only way to answer such questions is to do a lot of surveillance to look for exposures to these animal viruses, and I think that’s key to predicting future pandemics.”