Recall:
5 Oct: Police State: the avian flu excuse
http://www.cyberjournal.org/cj/show_archives/?id=655&lists=newslog
rkm
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http://www.nytimes.com/2005/10/06/health/06flu.html?th&emc=th
October 6, 2005
Experts Unlock Clues to Spread of 1918 Flu Virus
By GINA KOLATA
The 1918 influenza virus , the cause of one of history's most
deadly epidemics , has been reconstructed and found to be a
bird flu that jumped directly to humans, two teams of federal
and university scientists announced yesterday.
It was the culmination of work that began a decade ago and
involved fishing tiny fragments of the 1918 virus from
snippets of lung tissue from two soldiers and an Alaskan woman
who died in the 1918 pandemic. The soldiers' tissue had been
saved in an Army pathology warehouse, and the woman had been
buried in permanently frozen ground.
"This is huge, huge, huge," said John Oxford, a professor of
virology at St. Bartholomew's and the Royal London Hospital
who was not part of the research team. "It's a huge
breakthrough to be able to put a searchlight on a virus that
killed 50 million people. I can't think of anything bigger
that's happened in virology for many years."
The scientists painstakingly traced the genetic sequence,
synthesized the virus using tools of molecular biology, and
infected mice and human lung cells with it in a secure
laboratory at the Centers for Disease Control and Prevention
in Atlanta. The research is being published in the journals
Nature and Science.
The findings, the scientists say, reveal a small number of
genetic changes that may explain why this virus was so lethal.
It is significantly different from flu viruses that caused the
more recent pandemics of 1957 and 1968. Those viruses were not
bird flu viruses but instead were human flu viruses that
picked up a few genetic elements of bird flu.
The research also confirms the legitimacy of worries about the
bird flu viruses, called H5N1, that are emerging in Asia.
Since 1997, bird flocks in 11 countries have been decimated by
flu outbreaks. So far nearly all the people infected - more
than 100, including more than 60 who died - contracted the
sickness directly from birds. However, there has been little
transmission between people.
The 1918 virus, in contrast, was highly infectious, and in
recent weeks the fear that a transformation of one of the
current bird flus could make it infectious in humans has
prompted politicians of both major parties to scramble to
demonstrate that they are taking the threat of an avian flu
outbreak seriously.
Bush administration officials have been talking about pandemic
flu preparedness for years, and they say they will soon
release a pandemic flu plan, in the works for more than a
year. Senate Democrats say that the administration is not
doing enough, and they are writing their own bills that call
for more spending and coordination.
President Bush this week asked the leaders of the world's top
vaccine manufacturers - Chiron, Sanofi-Aventis, Wyeth,
GlaxoSmithKline and Merck - to come to the White House on
Friday to discuss preparations for pandemic flu, said people
with knowledge of the meeting who insisted on anonymity
because the White House has not yet announced the meeting.
The research on the 1918 virus is directly applicable to
current concerns, Dr. Anthony S. Fauci, director of the
National Institute of Allergy and Infectious Diseases, and Dr.
Julie L. Gerberding, director of the Centers for Disease
Control and Prevention, said in a joint statement. "The new
studies could have an immediate impact by helping scientists
focus on detecting changes in the evolving H5N1 virus that
might make widespread transmission among humans more likely,"
they said.
The bird flu viruses now prevalent share some of the crucial
genetic changes that occurred in the 1918 flu, scientists
said, but not all. The scientists suspect that with the 1918
flu, changes in just 25 to 30 out of about 4,400 amino acids
in the viral proteins turned the virus into a killer. The new
work also reveals that 1918 virus acts much differently from
ordinary human flu viruses. It infects cells deep in the lungs
of mice and infects lung cells, like the cells lining air
sacs, that would normally be impervious to flu. And while
other human flu viruses do not kill mice, this one, like
today's bird flus, does.
Other scientists said the new work was immensely important,
leading the way to identifying dangerous viruses before it is
too late and to find ways to disable them.
The 1918 flu, which killed as many as 50 million people
worldwide, showed how terrible that disease can be. It had
been "like a dark angel hovering over us," said Dr. Oxford,
the virology professor at St. Bartholomew's. The virus spread
and killed with terrifying speed, preferentially striking the
young and the healthy. Alfred W. Crosby, author of "American's
Forgotten Pandemic: The Influenza of 1918," said that it
"killed more humans than any other disease in a similar
duration in the history of the world."
The research, and its publication, raised concerns about
whether scientists should actually resurrect this killer that
vanished from the earth nearly a century ago.
"It is something we take seriously," said Dr. Fauci, whose
institute helped pay for the work. The work was extensively
reviewed, he added, and the National Science Advisory Board
for Biosecurity was asked to decide whether the results should
be made public. The board "voted unanimously that the benefits
outweighed the risk that it would be used in a nefarious
manner," Dr. Fauci said.
Others are not convinced.
Richard H. Ebright, a molecular biologist at Rutgers, said he
had serious concerns about the reconstruction of the virus.
"There is a risk verging on inevitability, of accidental
release of the virus; there is also a risk of deliberate
release of the virus." And the 1918 flu virus, Dr. Ebright
added, "is perhaps the most effective bioweapons agent ever
known."
But Dr. D. A. Henderson, a resident scholar at the University
of Pittsburgh Center for Biosecurity and a leading expert on
bioterrorism, said he agreed with the decision to reconstruct
the virus and publish its genetic sequence. "This work is of
the greatest importance, and it is very important that it be
published," he said.
The story of the resurrection of the 1918 flu began in 1995.
Until then, scientists had thought the task hopeless. Viruses
had not been discovered in 1918, so no one had isolated and
saved the one that caused the flu.
But Dr. Jeffery Taubenberger, chief of the molecular pathology
department at the Armed Forces Institute of Pathology in
Washington, had an idea for finding that ancient virus. He
recalled that his institute had a warehouse of autopsy tissue,
established by President Lincoln.
Dr. Taubenberger investigated and found tissue from two
soldiers who died of the 1918 flu, one in Massachusetts , one
on Long Island. The tissue was snips of lung soaked in
formalin and encased in little blocks of wax. In that tissue
was the virus, broken and degraded, but there, untouched for
nearly 80 years.
Then Dr. Taubenberger received a third sample, from a woman
who had died in Brevig, Alaska , when the flu swept through
her village, killing 72 adults and leaving just five. The dead
were buried in a mass grave in the permafrost. A retired
pathologist, Johan Hultin, hearing of Dr. Taubenberger's
quest, had traveled from his home in San Francisco at his own
expense. He dug up the grave with the villagers' permission,
extracted the woman's still frozen lung tissue and sent it to
Dr. Taubenberger.
Dr. Taubenberger and his colleagues spent nearly a decade
carefully extracting and piecing together the viral genes,
like putting together a jigsaw puzzle. Along the way, they
published findings that they and others used to try to
understand the 1918 flu, but until now they had published only
the sequences of five of the eight genes that make up the
virus. The last three, which make up half of the virus's
length, are published today in their paper in Nature.
In August, Terrence M. Tumpey of the Centers for Disease
Control and his colleagues used the viral genome to
reconstruct the 1918 virus, and they wondered what would
happen if they infected mice and if they infected tissue from
human lungs. And, they asked, would the virus remain as lethal
if they switched some of its genes with genes from today's
influenza viruses?
The scientists took great precautions, Dr. Gerberding said,
using special labs that were designed to protect the
researchers and prevent the spread of the viruses. "We have
erred on the side of caution at every step of the process,"
she added.
And now, the scientists say, the work is starting to unmask
that virus's secrets.
In gene-swapping experiments, the scientists found that small
substitutions weakened the reconstructed virus so that it
could no longer replicate in the lungs of mice, kill animals,
or attach itself to human lung cells in the lab.
The ultimate goal, Dr. Taubenberger says, is to make a
checklist of changes to look for in the bird viruses. "Now you
have all these viruses going around and we don't know, is it
going to adapt to humans? Is it going to cause a pandemic? We
don't understand the rules," he said. "There is a lot of
science to go."
Gardiner Harris contributed reporting from Washington for this
article.
Copyright 2005 The New York Times Company
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