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Biotech / Medical : Biotech Valuation -- Ignore unavailable to you. Want to Upgrade?

To: Doc Bones who wrote (13403)	10/7/2004 2:11:04 PM
From: Doc Bones	Respond to of 52153

Critical Gene a Suspect in Lethal Epidemic [NYT] By NICHOLAS WADE Published: October 7, 2004 By recreating the influenza virus that killed up to 50 million people in 1918-19, researchers may have identified the gene that turned it into one of the most lethal in human history. The gene, one of eight in the virus, seems to have an unexpected capacity for sending the body's immune system into overdrive, causing inflammation, hemorrhage and death, the scientists report today in the journal Nature. The research team, led by Dr. Yoshihiro Kawaoka of the University of Wisconsin, has been trying to determine just why the 1918 virus was so lethal and how defenses could be devised if a similar virus appeared in the future. Although the virus has long since perished, Dr. Kawaoka and his colleagues were able to recreate it because the composition of its genes had been reconstructed from the preserved tissue of victims. The genes have been reconstituted over the last few years by Dr. Jeffery K. Taubenberger and colleagues at the Armed Forces Institute of Pathology in Washington. Dr. Kawaoka, Dr. Taubenberger and others have been reinserting the 1918-type genes into ordinary flu viruses to see if they can pinpoint which of the genes made the virus so lethal and how it did so. In the latest of these experiments, which Dr. Kawaoka reports today, a gene called the hemagglutinin or HA gene seems to be largely responsible for the dire effects of Spanish flu, as the 1918 epidemic is also known. Recreating such a dangerous organism is not an experiment to be undertaken lightly. Dr. Kawaoka's approach required replacing the HA and another gene in a mild flu virus with the Spanish flu versions and infecting mice with the novel agent. Because of the obvious hazards, he at first conducted the work in the most secure type of biological laboratory, designated Biosafety Level 4, one of which was available at the National Microbiological Laboratory in Winnipeg, Canada. He said that after satisfying himself that the souped-up virus was susceptible to an antiviral agent known as Tamiflu, he transferred the research to a Biosafety Level 3 laboratory at the University of Wisconsin. Dr. R. Timothy Mulcahy, chairman of the university's biosecurity task force, said that the chances of escape from the Biosafety Level 3 facility were minimal and that Dr. Kawaoka had been "extremely prudent" in starting out at the higher level. "If there were an escape there would be treatments," Dr. Mulcahy said. He noted that another group of researchers had already worked with similar engineered flu viruses in a Level 3 facility owned by the Department of Agriculture in Athens, Ga. The HA gene studied by Dr. Kawaoka's team is well known to flu experts because it changes from year to year. Since the protein made by the gene is the one singled out for attack by the immune system, the body's defenses are caught off guard each year as flu virus arrives with a novel version of the protein to which the body has no prior immunity. The HA protein's role is to latch onto the surface of human cells and then help the virus merge into the cell's outer membrane. Researchers recently worked out the exact three-dimensional structure of the Spanish flu version of the HA protein, but could see no other function that it was designed to serve. The same is true of the other Spanish flu genes recovered by Dr. Taubenberger. In the current state of knowledge, the genes betray no clear hint of what makes them so lethal. That makes necessary experiments like Dr. Kawaoka's, in which researchers physically reconstruct the virus and try to understand how it works. What he has now found is that the Spanish flu version of the HA gene, in addition to its break-in and enter role, seems able to trigger the release of cytokines, the signaling agents with which the immune system gears itself up for massive attack against an infectious agent. Uncontrolled overdrive can make the immune system kill the body in order to save it, through excessive inflammation. The virus carrying the Spanish flu version of the HA gene produced high levels of cytokines in mice, Dr. Kawaoka says, and this is probably what led to the inflammation and lung damage that killed them. Dr. Adolfo Garcia-Sastre, a flu expert at the Mount Sinai School of Medicine who has constructed a similar virus, said the HA gene might be causing extra virulence simply by helping the virus replicate better, not because of any special effect on cytokine production. But either way, the finding helped focus attention on the gene's role, he said. Survivors of the 1918 epidemic have high levels of antibody to the engineered virus, Dr. Kawaoka reports, but people infected recently with a similar class of flu virus do not. "Thus, a large section of the population would be susceptible to an outbreak of a 1918-like influenza virus," he and his colleagues conclude. nytimes.com

To: Doc Bones who wrote (13403)	10/7/2004 2:21:53 PM
From: zeta1961	Respond to of 52153

Zeta, as long as we're ranting... Doc I rest my case Doc<g>...thanks for posting that one.. Really end of rant..have to figure out where I'm going to watch fleetweek.. Zeta@theLiberalIdealistandInnerConservativeRantingNurseBiofreak.org :)

To: Doc Bones who wrote (13403)	10/7/2004 10:09:29 PM
From: FiloF	Respond to of 52153

More on Chiron from WSJ. [That AG Edwards analyst is apparently a Master of the Obvious (Flu vaccines are a cyclical business. Failing to maximize profit at the top of a cycle is a cardinal error.] Chiron Flap Highlights; Primitive Vaccine Methods By MARILYN CHASE and PUI-WING TAM Staff Reporters of THE WALL STREET JOURNAL October 8, 2004 online.wsj.com Despite Chiron Corp.'s current nightmare with bacteriological contamination at its plant in Liverpool, England, the biotechnology pioneer is expected to push ahead in the relatively primitive business of making flu vaccines that provide a large chunk of its revenue. But even if Chiron can fix the problems at the Liverpool plant, which British regulators shut this week because of contamination concerns, the Emeryville, Calif., firm that discovered the hepatitis C virus will still be stuck for years to come making flu vaccines with 50-year-old methods using cultured chicken eggs, industry experts say. Chiron's flu-virus debacle illustrates a basic conundrum that it and other biotech companies continue to face: Modern gene-splicing techniques still aren't advanced enough to turn out vaccines in volume, so companies must rely on age-old, low-tech methods to produce many of today's drugs. Clearly, the debacle will have a short-term financial impact on Chiron, particularly since vaccines made up the bulk of the company's revenue. Last year, vaccines contributed $678 million to the company's overall $1.8 billion in revenue. Fluvirin, Chiron's flu vaccine for the U.S., generated $219 million last year and was expected to contribute about $300 million in sales this year. The company has cut its earnings guidance for the year to operating profits of between 70 cents to 80 cents, down from a previously projected $1.80 to $1.90. The company didn't give guidance for 2005, and also won't comment on whether it will undergo layoffs or reshuffle management, said John Gallager, a spokesman at Chiron. United Kingdom regulators who shut down a Chiron Corp. flu-vaccine plant this week found a litany of infractions there, said people familiar with their inspection report: vaccine lots contaminated with the bacteria serratia, problems with temperature control, and general concerns about sterility at the Liverpool plant whose license was revoked Tuesday. Neither U.S. officials nor Chiron have publicly questioned the U.K. regulators' findings. It is likely that none of the Chiron vaccine will be usable, though officials haven't ruled out trying to salvage some by additional cleansing. Food and Drug Administration scientists arrived in England yesterday to meet with U.K. regulators and Chiron officials, and tour the Liverpool plant this weekend. The FDA team is trying to assess the basis for the U.K. authorities' findings, Chiron's alleged failure to ensure sterility, and weigh potential lapses in "the entire context of good manufacturing practices that led them to suspend the license," said William Egan of FDA's vaccine branch. In the weeks before the shutdown, the company had told U.S. officials that some of the batches of the flu vaccine were testing negative for contamination with serratia. But it is unclear whether even lots that tested negative would be safe if the entire Chiron manufacturing process is flawed. Wall Street analysts add that they are now looking for the company to quickly resolve its issues with British regulators and to get its plant in Liverpool working again. "It's a tricky time for them," says Alex Hittle, an analyst at AG Edwards. "Flu vaccines are a cyclical business. Failing to maximize profit at the top of a cycle is a cardinal error." Chiron remains committed in the "long term" to the flu vaccine market in the U.S., said Mr. Gallager, the spokesman. In 2003, Chiron plunked down about $900 million in cash for Powderject Pharmaceuticals PLC, a British vaccine maker whose Liverpool factory Chiron inherited in the acquisition. The purchase was designed to boost Chiron's earnings through 2005, as the company sought new growth opportunities. In particular, Chiron has its eye on producing cell-culture vaccines, a modern method of developing vaccines that is potentially much more efficient and profitable. But cell-culture technology isn't expected to be filed for regulatory approval in Europe until 2006 at the earliest, so vaccine production using the method couldn't be available until 2007 or 2008. Meanwhile, Chiron has committed roughly $100 million to modernize and expand the Liverpool facility, industry analysts say. Chiron's vaccines bet suddenly looks riskier than ever.