November 2, 2004
By Doug Moe
Madison.com
I KNOW, I know. You already have plenty to worry about. The gutters on your house are full of leaves, the Bowl Championship Series has been punking the Badgers, and if you hear one more negative campaign ad on radio or TV, you're going to hurt somebody.
You probably don't need to hear that a British scientific journal just listed Madison as ground zero for a plague that, when last unleashed on the world, killed 40 million people.
That's tough news to read on a Monday, I'll grant you, though on the other hand it does make the annoying rattle behind the glove compartment in your car seem kind of unimportant.
The Oct. 23 issue of New Scientist included an article by Debora McKenzie headlined: "Could 1918 flu virus escape from labs?" The subhead on McKenzie's article said this: "Scientists experimenting on reconstructions of the lethal pandemic virus are accused of compromising on safety."
UW-Madison scientist Yoshihiro Kawaoka has been conducting experiments in his laboratory here on the so-called Spanish flu of 1918, which killed tens of millions around the world and more than 600,000 people in the United States.
Kawaoka is a virologist respected around the world for his research into the mysterious origins and spread of various kinds of influenza. Results of his experiments are regularly reported in both the scientific trades and the popular press.
Early last month, Kawaoka was again in the news when he published an article in the science journal Nature announcing he had isolated a gene that, in mice, turned an ordinary flu into the horrific flu of the 1918 pandemic.
The Oct. 23 New Scientist story is not the kind of notice Kawaoka usually receives. The story begins: "The 1918 flu virus spread across the world in three months and killed at least 40 million people. If it escaped from a lab today, the death toll would be far higher. 'The potential implications of an infected lab worker - and spread beyond the lab - are terrifying,' says D.A. Henderson of the University of Pittsburgh, a leading biosecurity expert.
"Yet despite the danger," the story continues, "researchers in the U.S. are working with reconstructed versions of the virus at less than the maximum level of containment. Many other experts are worried about the risks. 'All the virologists I have spoken to have concerns,' says Ingegerd Kallings of the Swedish Institute for Infectious Disease Control in Stockholm, who helped set laboratory safety standards for the World Health Organization."
New Scientist goes on to say that the most recent research is being done by Kawaoka in Madison.
"The latest work was done by Yoshihiro Kawaoka at the University of Wisconsin at Madison. His team showed that adding the 1918 gene for the surface protein haemagglutinin to modern viruses made them far deadlier to mice. The researchers also found that people born after 1918 have little or no immunity."
The magazine then notes - and this is the crux of the story - that the lab in Madison has a lower biosecurity level - BLS - than a very few other labs that have the highest possible levels of containment. The highest level is BSL-4. The Madison lab is BSL-3Ag, or 3-plus. New Scientist notes: "The main difference between BSL-4 and BSL-3Ag is that precautions to ensure staff do not get infected are less stringent: While BSL-4 involves wearing fully enclosed body suits, those working at BSL-3Ag labs typically have half-suits."
New Scientist did note that Kawaoka "is considered unusually cautious" by his colleagues. And he told the magazine that an antiviral drug, oseltamivir, given in advance to the mice in the experiment, had prevented them from getting sick. "This means," New Scientist quoted Kawaoka as saying, "that if all lab workers take oseltamivir 'they cannot become infected.' "
The magazine, though, followed that with this: "Yet this assumes that the mouse results apply to humans."
New Scientist then quoted a UK expert, John Wood of the National Institute for Biological Standards and Controls, saying, "We would do any such work at BSL-4."
New Scientist notes that "the recent SARS escapes were from BSL-3 labs."
I tried to reach Kawaoka by phone most of last week, but he was traveling outside the country. Over the weekend he sent me an e-mail strongly stating his belief that the Madison lab is safe. "Experiments with these viruses can be safely performed under BSL-3 conditions," Kawaoka wrote. He listed 13 specific safety practices including the taking of the antiviral drug by all personnel working with the virus; powered air purifying respirators with face shields; and showering and the removal of personal clothing by personnel in outer changing rooms.
"In addition," Kawaoka wrote me, "because we also work with pathogens identified by the U.S. government as select agents (i.e., highly pathogenic avian influenza viruses), our BSL-3 labs are highly secure. Access is strictly limited (identification card swipe and key restrictions) and only personnel that have satisfied FBI background checks can work in the labs. ... Our work with influenza viruses that contain 1918 virus genes is conducted under strict biosecurity."
Kawaoka concluded: "At the last biosafety meeting of the NIH Recombinant DNA Advisory Committee, which was held Sept. 21-22, 2004, I presented our risk assessment of our work on influenza viruses. No concern was raised by any of the committee members that attended this meeting regarding our decision to work with these viruses under BSL-3 conditions."
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