Big breakthrough on the 1918 flu virus!

[Guest guest]

Hi, all.

This is a very big deal. This article is from the New York Times.

The work described in it should supply information that will be a

big help in figuring out how to protect literally the whole world

against an avian flu pandemic. Hooray for the Armed Forces Institute

of Pathology and the CDC!! I think they did something really good

this time. Yes, there's the risk of it getting loose, and yes,

there's the risk of a megalomaniac synthesizing it and releasing it,

but I can't imagine that that would fulfill anyone's goals, whoever

they might be, because those doing it would be at risk as much as

everyone else, and their name would live in infamy, not in glory,

among the survivors around the world. In the meantime, there's the

opportunity for the " good guys " to figure out how to make a vaccine

against it. Yes, I still do think that there are some " good guys. "

Rich

October 5, 2005

Deadly 1918 Epidemic Linked to Bird Flu, Scientists Say

By GINA KOLATA

Two teams of federal and university scientists announced today that

they had resurrected the 1918 influenza virus, the cause of one of

history's most deadly epidemics, and had found that unlike the

viruses that caused more recent flu pandemics of 1957 and 1968, the

1918 virus was actually a bird flu that jumped directly to humans.

The work, being published in the journals Nature and Science,

involved getting the complete genetic sequence of the 1918 virus,

using techniques of molecular biology to synthesize it, and then

using it to infect mice and human lung cells in a specially

equipped, secure lab at the Centers for Disease Control and

Prevention in Atlanta.

The findings, the scientists say, reveal a small number of genetic

changes that may explain why the virus was so lethal. The work also

confirms the legitimacy of worries about the bird flu viruses that

are now emerging in Asia.

The new studies find that today's bird flu viruses share some of the

crucial genetic changes that occurred in the 1918 flu. 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 bird flus, known as H5N1 viruses, have a

few, but not all of those changes.

In a joint statement, Dr. Fauci, director of the National

Institute of Allergy and Infectious Diseases, and Dr.

Gerberding, director of the Center for Disease Control and

Prevention, said, " The new studies could have an immediate impact by

helping scientist focus on detecting changes in the evolving H5N1

virus that might make widespread transmission among humans more

likely. "

The work also reveals that the 1918 virus is very different 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

normally would be impervious to flu. And while other human flu

viruses do not kill mice, this one, like today's bird flus, does.

But Dr. Jeffery Taubenberger, chief of molecular pathology

department at the Armed Forces Institute of Pathology, notes that

the bird flus have not yet spread from human to human. He hopes the

1918 virus will reveal what genetic changes can allow that to

happen, helping scientists prevent a new pandemic before it starts.

Scientists said the new work was immensely important, leading the

way to identifying dangerous viruses before it is too late and to

finding ways to disable them.

" This is huge, huge, huge, " said Oxford, a professor of

virology at St. Bartholmew'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 1918 flu showed how terrible that disease could be. It had

been " like a dark angel hovering over us, " Dr. Oxford said. The

virus spread and killed with terrifying speed, preferentially

striking the young and the healthy. Alfred C. Crosby, author

of " America's Forgotten Pandemic: The Influenza of 1918, " wrote that

it " killed more humans than any other disease in a similar duration

in the history of the world. "

But the research, and its publication, also raised concerns about

whether scientists should publish the genetic sequence of the 1918

virus. And should they actually resurrect a killer that vanished

from the earth nearly a century ago?

" It is something we take seriously, " said Dr. Fauci of the National

Institute of Allergy and Infectious Diseases, which helped pay for

the work. The work was extensively reviewed, he added, and the

National Scientific 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 sanguine.

H. Ebright, a molecular biologist at Rutgers University,

said he had concerns about the reconstruction of the virus and about

publication of procedures to reconstruct 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, " he said, adding

that the 1918 flu virus " is perhaps the most effective bioweapons

agent ever known. "

But Dr. D. A. , a resident scholar at the Center for

Biosecurity at the University of Pittsburgh 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, " he said, " and it is very

important that it be published. "

The story of the resurrection of the 1918 flu began in 1995, when

Dr. Taubenberger had an idea. He knew about the 1918 flu and the

horrors of that pandemic. Medical authorities at the time found it

hard even to describe the devastation. At Fort Devens, wrote one

doctor, Victor Vaughan, they saw young soldiers' " bodies stacked

like cordwood, " dead from the flu. The epidemic, he added, " visited

the remotest corners, taking toll of the most robust, sparing

neither soldier nor civilian, and flaunting its red flag in the face

of science. "

It had seemed hopeless, though, to discover what that virus looked

like. Viruses had not been discovered in 1918 and so no one had

isolated and saved the one causing that flu. But Dr. Taubenberger

recalled that his institute had a warehouse of autopsy tissue,

established by President Abraham Lincoln, who had ordered that every

time a military doctor examined a patient and took a tissue sample,

a sample must also be sent to and stored at the pathology institute.

Dr. Taubenberger wondered if he could find lung tissue from soldiers

who died of the 1918 flu and, if so, if he could extract the virus.

He found tissue from two soldiers, snips of lung soaked in formalin

and encased in little blocks of wax. And in that tissue was the

virus, broken and degraded, just a few molecules of virus, but

there.

One of the patients was Roscoe Vaughan, who got the flu when he was

21 years old and training at Camp , S.C. On Sept. 19, 1918,

he reported to sick call. He died on Sept. 26, unable to breathe,

the air sacs in his lungs filled with fluid. The other patient was

Down, age 30, who died on the same day at Camp Upton, in New

York. The snippets of their lung tissue had remained untouched for

nearly 80 years.

Then Dr. Taubenberger got a third sample, from a woman who had died

in Alaska when the flu swept through her village, killing 72 adults,

leaving just 5. The dead were buried in a mass grave in the

permafrost, and a retired pathologist, Johann Hultin, hearing of Dr.

Taubenberger's quest, traveled from his home in San Francisco to the

gravesite in Alaska at his own expense, dug up the grave with the

villager's 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 only published the sequences of five of the eight

genes. The last three, which make up half the virus's length, are

published in their paper, in Nature.

In August, Terrence M. Tumpey of the Centers for Disease Control and

his colleagues used that information to reconstruct the 1918 virus

and ask 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, the director of the C.D.C.,

Gerberding, said at a news conference, 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, " Dr. Gerberding said.

And now, the scientists say, they are starting to unmask that

virus's secrets.

In gene-swapping experiments, for example, they put the

hemagglutinin gene from the 1918 virus for one from a more recent

human virus. Suddenly, the reconstructed virus could no longer

replicate in the lungs of mice and no longer killed the animals. It

also could not attach itself to human lung cells in the lab. Yet the

1918 virus' hemagglutinin protein differs in just two critical amino

acids from the protein of a typical avian flu virus.

" Now we've shown experimentally that those two changes are crucial

for human adaptation, " Dr. Taubenberger said. So far, he added, they

have not been seen in the Asian bird flus.

The ultimate goal, he 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, " Dr. Taubenberger said. " There is a lot

of science to go. "