Thursday, January 18, 2007

all in the name of science

i like the commentary additives from CLG:

Scientists recreate 1918 flu virus [Why?] 17 Jan 2007 The virus that caused the 1918 influenza pandemic triggered an overwhelming immune response that swamped the lungs of macaque monkeys — the first primates deliberately infected with the Spanish flu virus, Canadian and American scientists reported Wednesday. The research, published in the journal Nature, involved an ambitious project to painstakingly recreate the 1918 virus — only the second time this feat has been achieved. In 2005 scientists at the U.S. Centers for Disease Control made history by becoming the first team to recreate the virus. Yoshihiro Kawaoka, a leading influenza scientist working at the University of Wisconsin, Madison, built each of the virus's eight genes from scratch, using genetic blueprints housed in a public access database... The recreated virus was then used to infect seven macaques housed in a Level 4 laboratory in Winnipeg — the highest level of biosecurity available. [Bush is poised to play the bioterror card, impose martial law, stuff any dissenters in a KBR detention centre and invade any oil-bearing country for Cheney Halliburton, unmolested. --LRP]

'The first the we do, let's kill all the lawyers.' - Henry VI part II, act IV, scene II --William Shakespeare


Scientists Recreate 1918 Flu and See Parallels to Bird Flu --In 2005, U.S. Army scientists reconstructed Spanish flu virus by extracting genetic fragments from the bodies of victims exhumed from the Alaskan permafrost. 18 Jan 2007 Scientists infected monkeys with a virus that caused the 1918-19 influenza pandemic and said in the Jan. 18 issue of the journal Nature that it caused an illness like that suffered by patients with the bird flu now spreading in Asia.


1918 flu virus triggers overwhelming immune response
Canadian Press 17/01/07

The virus that caused the 1918 influenza pandemic triggered an overwhelming immune response that swamped the lungs of macaque monkeys — the first primates deliberately infected with the Spanish flu virus, Canadian and American scientists reported Wednesday.

The research, done in part at the Public Health Agency of Canada's National Microbiology Laboratory in Winnipeg, supports the notion that the virulent flu virus turned the body's immune system against itself. Scientists believe that theory explains how the devastating influenza strain managed to mow down unprecedented numbers of healthy people in the prime of life.

Previous work, done by some of the same scientists, showed mice infected with the virus also experienced this hyper immune response, a so-called cytokine storm. (Cytokines are one of the proteins the immune system makes to fight infection.)

“There was an uncontrolled or aberrant inflammatory response,” one of the authors, Dr. Michael Katze of the University of Washington in Seattle, explained in a telephone briefing.

“One possibility (is) . . . instead of protecting the individuals that were infected with the highly pathogenic virus, the immune response is actually contributing to the lethality of the virus.”

Discovering how the Spanish flu, an H1N1 virus, killed an estimated 50 million people around the globe isn't an exercise in archeological microbiology. Cracking the mysteries of highly virulent flu strains could help the world prepare to battle the next bad influenza pandemic, said Darwyn Kobasa, a research scientist with the Winnipeg lab and the first author on the paper.

“Not only is the study of interest to understand what happened in 1918 but it's also very relevant today as we possibly prepare for a new influenza pandemic caused by an avian H5N1 virus,” said Mr. Kobasa, referring to the highly pathogenic flu strain that for more than three years has been decimating poultry flocks in parts of Asia and which has killed over 160 people.

“The H5N1 virus can also cause very serious disease and it appears to do this in a way that's quite similar to the 1918 virus. We think that a greater understanding of the viruses that caused past pandemics will help us predict what might be expected and how to plan to use our knowledge and resources to reduce the impact of a new pandemic.”

The research, published in the journal Nature, involved an ambitious project to painstakingly recreate the 1918 virus — only the second time this feat has been achieved. In 2005 scientists at the U.S. Centers for Disease Control made history by becoming the first team to recreate the virus.

The effort that led to this research began a short time later. Yoshihiro Kawaoka, a leading influenza scientist working at the University of Wisconsin, Madison, built each of the virus's eight genes from scratch, using genetic blueprints housed in a public access database.

He then gave the plasmids — the pieces of DNA in which the genes were placed — to scientists in Winnipeg. They then transferred or “transfected” the genes into cell culture, allowing them to reassemble and grow in a process called virus “rescue.”

The recreated virus was then used to infect seven macaques housed in a Level 4 laboratory in Winnipeg — the highest level of biosecurity available. The monkeys became so ill they were euthanized after eight days, at which point lung and other tissues were analyzed to chart the damage done.

Dr. Katze and his team in Seattle also traced the immunologic system response by analyzing which immune proteins were produced when, and to what levels.

Scientists hope that learning which parts of the immune system overreact to this or other virulent flu viruses could provide clues as to how the process could be interrupted and the damage lessened.

“It suggests if you interrupt the inflammatory chain in the innate immune response, then you might have another tool in your armamentarium,” said Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases and an expert in the workings of the immune system.

But while this work is a start, scientists still don't know how to dampen down the immune response without then letting the virus continue to multiply unchecked.

“If the result is, OK, you get less cytokines which will be good in terms of immunopathology — but because of that you get also even higher levels of virus replication which results in tissue damage, then you've solved one problem but you come out with another one,” said Adolfo Garcia-Sastre, the microbiologist at New York's Mt. Sinai Medical Center who played an instrumental role in the first project to recreate the 1918 virus, but who was not involved in this study.

Scientists Recreate 1918 Flu and See Parallels to Bird Flu
BLOOMBERG NEWS January 18, 2007

Scientists infected monkeys with a virus that caused the 1918-19 influenza pandemic and said in the Jan. 18 issue of the journal Nature that it caused an illness like that suffered by patients with the bird flu now spreading in Asia.

Infection with a reconstructed version of the 1918 virus, known as the Spanish flu, incited a deadly chemical reaction in the laboratory animals, a group of scientists said in the magazine.

The group was led by Darwyn Kobasa, a researcher for the Public Health Agency of Canada in Winnipeg, Manitoba. Both the Spanish flu and H5N1 bird flu in Asia appear able to set off the reaction, the researchers said. Studying the Spanish flu virus’s interaction with monkeys may help health officials prepare for a possible pandemic caused by H5N1.

“We see responses that are similar between humans infected with H5N1 and nonhuman primates infected with the 1918 virus,” said Yoshihiro Kawaoka, a virologist at the University of Wisconsin in Madison. “By studying this model in detail, we may learn to cope with those immune responses.”

The 1918 flu may have killed as many as 50 million people, about 2 percent of those infected. Researchers say the outbreak started as a bird virus, until genetic changes enabled it to spread in people.

Similar mutations may allow H5N1 to set off a pandemic, researchers say. The bird flu has infected 267 people, mostly poultry workers or keepers in Asia, and killed 161 of them since late 2003, according to data compiled by the World Health Organization.

While the study points to an immune response as a probable cause for the destructiveness of the 1918 flu, researchers are still learning about the virus, said Michael Katze, a microbiologist at the National Primate Research Center at the University of Washington in Seattle.

“We know very little about why these viruses are so lethal,” Dr. Katze said.

Research has shown that H5N1 kills mice, causing the same kind of chemical reaction, called a cytokine storm, seen in the monkeys. Many other flu viruses are also fatal in mice, and the researchers said it was important to conduct studies in primates.

In 2005, Army scientists reported that they had reconstructed the Spanish flu virus by extracting genetic fragments from the bodies of victims exhumed from the Alaskan permafrost. American and Canadian researchers compared the effects of the virus on monkeys with those of seasonal flus.

The 1918 virus grew faster and spread more widely in the monkeys than the other viruses. While the immune reaction to the seasonal viruses abated after a few days, the response in monkeys with Spanish flu persisted, damaging tissues and impairing lung function, the study said.

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