Shiloh
Editor, Senior Moderator
Source: http://canadianpress.google.com/article/ALeqM5jhnMj6i16MEUtQiY1igFrH_TiXpA
Ninety years after killer virus roamed, scientists try to coax out its secrets
TORONTO ? In the fall of 1918, a seemingly simple influenza virus morphs into a mass murderer. Ninety years later, scientists are still flummoxed by why and how that happened.
But thanks to some impressive microbiological sleuthing - and the preservative powers of paraffin and permafrost - researchers are now studying the virus that caused the worst known infectious disease outbreak in history.
It's been three years since Dr. Terry Tumpey, a virologist working with the U.S. Centres for Disease Control, slipped eight individually reconstructed gene segments into a growth medium to see if they would knit together and essentially resurrect the killer of old.
Tumpey started that process on a Friday in the summer of 2005. By the Monday, he could see that scientific history had been made.
"It's pretty exciting to walk in the lab and look underneath the microscope and just like, wow, I got it. It's clear," he recalls.
Since Tumpey first "rescued" copies of the H1N1 virus that caused the Spanish flu, he and others have been studying its properties in a bid to figure out why the virus was so lethal.
They've swapped out individual genes, replacing them with ones from much milder contemporary H1N1 viruses. And then they've swapped them back in, all with the aim of trying to figure out which give the virus its virulence and which let what had likely been a bird virus start infecting people.
The hope is that by studying this virus - which was in the early stages of becoming a human virus - scientists will be able to figure out what it takes for any influenza virus to successfully make the leap to people from an animal host.
For decades, it had seemed study of the Spanish flu virus would never be possible. It was thought the virus itself had been lost to time.
It hadn't been isolated and preserved during the outbreak. Back then, scientists didn't even know viruses existed. They thought influenza was caused by a bacterium.
By the time the influenza virus was discovered in 1933, H1N1 viruses were still circulating. But they had mutated substantially in the intervening years, in the process losing whatever had made the virus so deadly.
In the 1950s, a Swedish doctoral student named Johan Hultin who was studying at the University of Iowa actually tried to find samples of the 1918 virus, travelling to an Alaskan community called Brevig Mission to exhume bodies of Spanish flu victims buried in the permafrost.
The community, called Teller Mission during the outbreak, had lost 70 of 110 residents to the flu in a single week in November 1918.
Hultin found preserved bodies and took pieces of lung tissue, but could not grow live viruses from the samples. At the time, that would have been the only way to capture the killer.
But by the late 1980s, science had learned how to crack genetic codes and how to fish out tiny fragments of genetic material from human tissues. Researchers no longer needed live viruses. With fragments of dead ones, genetic blueprints could be read and viruses could be reconstituted, gene by gene.
In 1995, a rising young scientist at the U.S. Armed Forces Institute of Pathology decided to try to do just that.
Jeffery Taubenberger, who didn't know about Hultin's earlier effort, set out to mine the institute's library of tissue samples taken from American soldiers who died while in the service. Paraffin-preserved lung tissue from soldiers who died of flu in 1918 might contain the genetic fragments needed to rewrite the genetic recipe for the virus, he thought.
An article in the journal Science alerted Hultin to Taubenberger's work. By then a pathologist practising in the San Francisco area, Hultin wrote to make an extraordinary offer: He would go back to Alaska to exhume more Spanish flu graves in the hopes of finding preserved lung tissue.
With the permission of the community, Hultin tried again, this time taking lung tissue from four corpses. And from one of those long-dead victims, Taubenberger's lab was able to retrieve pieces of the Spanish flu virus.
"Ultimately we have done partial sequence analysis from a number of cases of people who died after infection with the 1918 virus from three sources now," Taubenberger says. In addition to the material supplied by Hultin, samples from the Institute of Pathology's collection and a similar cache of preserved tissue at the Royal London Hospital yielded virus fragments.
In 2001, Taubenberger's team reported in the scientific literature that they'd sequenced the hemagglutinin gene of the 1918 virus, the gene that launches the attack on respiratory tract cells. In the fall of 2005 they published the sequences of the last three genes concurrently with Tumpey's report that the virus had been recreated.
It was an extraordinary scientific feat, one that took nine years of meticulous effort.
But while people like Tumpey and Taubenberger - now with the U.S. National Institute of Allergy and Infectious Diseases - are still trying to coax the virus's secrets from it, 90 years after the outbreak there remain more questions than answers.
"I think that it was a huge effort to actually sequence the virus but that wasn't, of course, the end of the story. So in a sense maybe it was sort of the end of the beginning. And now there's just a huge amount of work to go to understand what is encoded in those genes of the 1918 virus. What does that tell us about where the 1918 virus came from, why did it behave the way it did?" Taubenberger says.
"The sequence of the virus made it look just like a typical influenza virus, in a sense. There are unusual features about it, but in general there was nothing you could point your figure to and say 'Aha! Look! See that mutation right there? That was what was making it behave the way it did. This was why the virus was able to kill tens of millions of people."'
"And we still can't do that."
Ninety years after killer virus roamed, scientists try to coax out its secrets
TORONTO ? In the fall of 1918, a seemingly simple influenza virus morphs into a mass murderer. Ninety years later, scientists are still flummoxed by why and how that happened.
But thanks to some impressive microbiological sleuthing - and the preservative powers of paraffin and permafrost - researchers are now studying the virus that caused the worst known infectious disease outbreak in history.
It's been three years since Dr. Terry Tumpey, a virologist working with the U.S. Centres for Disease Control, slipped eight individually reconstructed gene segments into a growth medium to see if they would knit together and essentially resurrect the killer of old.
Tumpey started that process on a Friday in the summer of 2005. By the Monday, he could see that scientific history had been made.
"It's pretty exciting to walk in the lab and look underneath the microscope and just like, wow, I got it. It's clear," he recalls.
Since Tumpey first "rescued" copies of the H1N1 virus that caused the Spanish flu, he and others have been studying its properties in a bid to figure out why the virus was so lethal.
They've swapped out individual genes, replacing them with ones from much milder contemporary H1N1 viruses. And then they've swapped them back in, all with the aim of trying to figure out which give the virus its virulence and which let what had likely been a bird virus start infecting people.
The hope is that by studying this virus - which was in the early stages of becoming a human virus - scientists will be able to figure out what it takes for any influenza virus to successfully make the leap to people from an animal host.
For decades, it had seemed study of the Spanish flu virus would never be possible. It was thought the virus itself had been lost to time.
It hadn't been isolated and preserved during the outbreak. Back then, scientists didn't even know viruses existed. They thought influenza was caused by a bacterium.
By the time the influenza virus was discovered in 1933, H1N1 viruses were still circulating. But they had mutated substantially in the intervening years, in the process losing whatever had made the virus so deadly.
In the 1950s, a Swedish doctoral student named Johan Hultin who was studying at the University of Iowa actually tried to find samples of the 1918 virus, travelling to an Alaskan community called Brevig Mission to exhume bodies of Spanish flu victims buried in the permafrost.
The community, called Teller Mission during the outbreak, had lost 70 of 110 residents to the flu in a single week in November 1918.
Hultin found preserved bodies and took pieces of lung tissue, but could not grow live viruses from the samples. At the time, that would have been the only way to capture the killer.
But by the late 1980s, science had learned how to crack genetic codes and how to fish out tiny fragments of genetic material from human tissues. Researchers no longer needed live viruses. With fragments of dead ones, genetic blueprints could be read and viruses could be reconstituted, gene by gene.
In 1995, a rising young scientist at the U.S. Armed Forces Institute of Pathology decided to try to do just that.
Jeffery Taubenberger, who didn't know about Hultin's earlier effort, set out to mine the institute's library of tissue samples taken from American soldiers who died while in the service. Paraffin-preserved lung tissue from soldiers who died of flu in 1918 might contain the genetic fragments needed to rewrite the genetic recipe for the virus, he thought.
An article in the journal Science alerted Hultin to Taubenberger's work. By then a pathologist practising in the San Francisco area, Hultin wrote to make an extraordinary offer: He would go back to Alaska to exhume more Spanish flu graves in the hopes of finding preserved lung tissue.
With the permission of the community, Hultin tried again, this time taking lung tissue from four corpses. And from one of those long-dead victims, Taubenberger's lab was able to retrieve pieces of the Spanish flu virus.
"Ultimately we have done partial sequence analysis from a number of cases of people who died after infection with the 1918 virus from three sources now," Taubenberger says. In addition to the material supplied by Hultin, samples from the Institute of Pathology's collection and a similar cache of preserved tissue at the Royal London Hospital yielded virus fragments.
In 2001, Taubenberger's team reported in the scientific literature that they'd sequenced the hemagglutinin gene of the 1918 virus, the gene that launches the attack on respiratory tract cells. In the fall of 2005 they published the sequences of the last three genes concurrently with Tumpey's report that the virus had been recreated.
It was an extraordinary scientific feat, one that took nine years of meticulous effort.
But while people like Tumpey and Taubenberger - now with the U.S. National Institute of Allergy and Infectious Diseases - are still trying to coax the virus's secrets from it, 90 years after the outbreak there remain more questions than answers.
"I think that it was a huge effort to actually sequence the virus but that wasn't, of course, the end of the story. So in a sense maybe it was sort of the end of the beginning. And now there's just a huge amount of work to go to understand what is encoded in those genes of the 1918 virus. What does that tell us about where the 1918 virus came from, why did it behave the way it did?" Taubenberger says.
"The sequence of the virus made it look just like a typical influenza virus, in a sense. There are unusual features about it, but in general there was nothing you could point your figure to and say 'Aha! Look! See that mutation right there? That was what was making it behave the way it did. This was why the virus was able to kill tens of millions of people."'
"And we still can't do that."
