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  • “Any community that fails to prepare, with the expectation that the federal government or, for that matter, even the state government will come to their rescue at the final moment will be tragically wrong,” Michael Leavitt, Secretary of Health and Human Services

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October 29, 2007

Influenza Research

When I came to the issue of pandemic influenza I knew what amounted to nothing at all. My first year (2005) was spent doing little more than learning as much as I could. One of the first things that I learned was that I was not the only flu ignorant person, which given the pride I take in "knowing stuff" I found comforting. However, that comfort soon evaporated when I learned that even our "experts" suffered a shocking dearth of knowledge.

Not knowing something is one thing, admitting that you don't know it is something else, and given human nature, extremely difficult for most to do.

There is so much we don't know about the influenza virus, research lost out to the more lucrative and illustrious human diseases as cancer, AIDS/HIV, Ebola, Malaria, and Dengue. These diseases were more lucrative and illustrious because solving their puzzle, and finding their solutions, would make such a difference to the lives of so many who lived under their threat and here-and-now consequences.

That all changed in 2003 and by 2005 significant money began to flow. Along with the money our few virologists who had expertise in influenza began to enjoy a certain celebrity status. Suddenly influenza research was not some back country hinterland of infectious disease, but critical and pressing.

Much of what we have learned in these few intervening years has been just what we don't know, or what we thought we knew was wrong. As in much of science, each new piece of information leads to innumerable other questions clamoring to be explored and answered.

Today's news offered a piece that highlights the scramble to learn and one of our viral luminaries.

Flu lab set to open

By David Wahlberg
608-252-6125

dwahlberg@madison.com

Ten inch walls made with crack-resistant concrete. Outlets sealed with silicone.

Sensors for broken windows. Infrared surveillance beams. Redundant air handling systems. A back-up generator.

UW-Madison's $12.5 million Institute for Influenza Viral Research, nearing completion at University Research Park, will have a collection of safety and security features the university hasn't seen before.

Many people will be watching the work of the institute, to be directed by virologist Yoshihiro Kawaoka.

The observers include health officials, who want a better understanding of the bird flu virus that is threatening a global flu epidemic. They include scientists, who are competing with Kawaoka to make discoveries about bird flu and other flu viruses.

They also include critics, who have charged Kawaoka with circumventing safety rules.

Critics objected three years ago to Kawaoka 's research at UW-Madison involving the deadly 1918 flu virus, saying his safety measures were not strict enough.

This September, they revealed that the university halted his work on components of the Ebola virus last year after the National Institutes of Health said the studies must be done in a lab more secure than any on campus.

Without proper precautions, the critics say, such viruses can escape.

"It's a very significant and a very real risk," said Edward Hammond, of the Austin, Texas-based Sunshine Project, which released documents about the Ebola work. "They handle viruses that could kill tens of millions of people. "

Jan Klein, UW-Madison's biological safety officer, said Kawaoka and other researchers at the university take adequate measures to manage the risks.

Kawaoka said his detractors didn't understand the extent of the precautions he used for the 1918 flu virus research. After shifting the work to a higher-security lab in Canada, he started doing some of it again in Madison this year after the U.S. Centers for Disease Control and Prevention approved it.

He said the guidelines regarding the Ebola research, which he hasn't resumed in Madison, are open to interpretation. Klein said the university may appeal the NIH's ruling about the Ebola work.

Kawaoka, a prominent and prolific flu researcher, was being wooed to the University of Pittsburgh until UW-Madison promised him the new institute. The 28,000-square-foot facility on Science Drive, to be finished next month, will enable him to expand his studies, he said.

Kawaoka plans to study several kinds of flu viruses in the institute -- including H5N1, the bird flu virus circulating in Asia, and a reconstructed version of the 1918 flu virus, which killed some 50 million people when it spread worldwide.

"Space has been a limiting factor for our research," Kawaoka said of the School of Veterinary Medicine lab he has been using. "Now we'll be able to do multiple experiments at the same time. We want to show people that the work we do is safe. "

BSL3-Ag

The institute contains lab space classified as Biosafety Level 3-Agriculture, a standard higher than any other lab at the university. BSL3-Ag is near the top of the federal government's four-level scale for labs involving infectious agents.

Only a few BSL-4 labs, in which workers don space suits with self-contained breathing devices, exist nationwide.

Several labs at UW-Madison, including some of Kawaoka's lab space in the veterinary school, are BSL-3. In those labs, researchers wear gloves and masks and work under cabinets, and the air is specially filtered.

The BSL-3 Ag designation carries additional requirements, such as extra air handling systems, showers upon leaving the lab -- and in the case of bird flu research, no contact with birds for several days.

Additional features also will ensure safety, said James Corkery, president of ACS. The Madison construction management company is overseeing the remodeling of a former office building, last used by Epic Systems, to create the institute.

Corkery said the steel airlock door used to enter the BSL-3 Ag lab is welded to its frame, like in a submarine.

He said petri dishes, animal cages and other lab equipment will be washed and run through autoclaves, sterilizing machines that use heat and pressure to kill germs. Liquid waste will be cooked in a separate system at 250 degrees Fahrenheit for an hour before flowing into the sewer system.

"Nothing can live after that," Corkery said, pointing to steam tanks surrounded by stainless steel pipes in the institute's basement.

The $12.5 million cost -- up from the $9 million cited when the university announced plans for the institute last year -- is being shared, roughly equally, by UW-Madison and the Wisconsin Alumni Research Foundation, the university 's tech-transfer agency.

Only one other BSL-3 Ag lab exists in Madison, at the National Wildlife Health Center off Schroeder Road.

CDC inspection

Though Kawaoka said he is eager to move his 18-person lab group into the institute and hire more researchers, the shift may not happen for months.

In order for him to use the H5N1 virus or the 1918 virus in the new building, the CDC must first inspect the lab and grant approval. The agency may visit in late November.

When Kawaoka applied for similar approval at his existing lab, it took a year, he said.

CDC permission to use the new space "could take weeks, months or even one year," he said. "I don't expect it to be done within this year. "

Much of the research in the institute will involve animals. Rooms are available for rodents, ferrets, poultry and monkeys.

Initially, Kawaoka said, he'll continue three research areas: studying how and why the H5N1 virus, the 1918 virus and other flu viruses are virulent, improving techniques for making flu vaccines and screening compounds that could lead to new antiviral drugs against flu.

Though bird flu has dropped off the national news radar, Kawaoka said its threat of causing a pandemic continues. The virus has killed 204 of the 332 people known to be infected since 2003, mostly in Asia, including 31 deaths in Indonesia this year.

A single genetic change could make the virus capable of spreading easily among people, Kawaoka said. If that happens, experts say the virus could be more dangerous than the 1918 flu.

H5N1 "is still spreading," Kawaoka said. "It's becoming more human-like."

Another lab in Madison continues to be closely involved in surveillance for bird flu and regular flu. The Wisconsin Laboratory of Hygiene, part of UW-Madison, is one of three labs in the country to use a new kind of test to evaluate regular flu samples for resistance to certain antiviral drugs. The testing began last year and will continue this flu season. The state lab has worked with 130 hospital and clinical labs throughout the state to prepare a flu pandemic checklist. Erik Reisdorf, a microbiologist at the lab, has traveled to India and Thailand to train scientists to use new molecular techniques to test samples for H5N1, the bird flu virus, and other types of flu. 

  --David Wahlberg

One of my favorite sayings is "We live, we learn, we move forward".

SZ

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Comments

Nice post SZ! When I first read of Yoshihiro Kawaoka, I was intrigued by the specific nature of his research. Finally someone was going to get inside this virus to find out what makes it tick. Frustrating though to read it may be another year to get final approval from the CDC to open his new biolab at a time when his kind of research is most needed now.

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