Wisconsin lab broke Ebola rules, watchdog group says

Sep 25, 2007 (CIDRAP News) – Researchers at the University of Wisconsin at Madison (UW-Madison) worked on Ebola virus genetic material in a lab that lacked the required security measures, and federal agencies responsible for monitoring compliance didn't notice the problem, a watchdog group that monitors biodefense research safety reported recently.

UW-Madison's institutional biosafety committee (IBC) wrongly allowed well-known influenza researcher Yoshihiro Kawaoka to work with Ebola genetic material in a biosafety level 3 (BSL-3) lab, though federal rules require use of a BSL-4 lab for such work, the Sunshine Project, based in Austin, Tex., reported on Sep 19. BSL-4 is the highest biosecurity rating.

The university stopped the research in October 2006 after the National Institutes of Health (NIH) said a BSL-4 lab was required, even though the university disagreed, according to UW-Madison officials. The NIH was funding the research.

Ebola is a highly contagious virus that causes a hemorrhagic fever and is lethal in about 50% to 90% of cases. Because the Ebola virus is so dangerous, the US government lists it as a category A bioterrorism agent. There is no vaccine or specific treatment for the disease.

The Web site for Kawaoka's lab says that in addition to work on influenza viruses, researchers are exploring the molecular pathogenesis of the Ebola virus and have established a reverse-genetics system for generating the virus, which they hope to use for vaccine production and the identification of antiviral medication targets.

The Web site emphasizes that the lab has developed a novel complement system that allows researchers to study Ebola virus glycoproteins without having to do the work in a BSL-4 lab.

Researcher sought lighter restrictions
The Sunshine Project's report makes it clear that Kawaoka and his colleagues weren't working with live Ebola virus, but rather full-length copies of Ebola DNA (complementary DNA, or cDNA) that lacks two critical proteins that could trigger growth of an infectious virus. However, the group says that federal rules require use of a BSL-4 lab for handling Ebola virus genetic material "that has not been rendered irreversibly incapable of reproducing."

The rule violation came to light only after Kawaoka asked permission to do the work in a BSL-2 lab, which prompted Jan Klein, UW-Madison's biological safety officer, to seek guidance from the NIH, according to e-mail messages posted on the Sunshine Project's Web site. The NIH responded that studies with the Ebola material should be conducted in a BSL-4 lab, which UW-Madison does not have.

Edward Hammond, Sunshine Project director, said in the press release that the NIH's response amounts to disapproving its own project. "It is dismaying but not surprising that NIH's biodefense program was funding work that violates NIH's safety rules. The guidelines have been an unenforced afterthought for years," he said.

The violation apparently was not noted by staff from the US Centers for Disease Control and Prevention's (CDC's) Select Agent Program, which inspected Kawaoka's lab, the Sunshine Project said.

UW official sees inconsistent rules
In an interview with CIDRAP News, James W. Tracy, associate dean of research in the School of Veterinary Medicine at UW-Madison, defended Kawaoka's request to do the work in a BSL-2 lab as reasonable. "He made the request based on facts that his colleagues at the CDC are working with the same material under BSL-2 conditions," he said. Kawaoka's lab is part of the veterinary school.

The main problem stems from differences in how research facilities interpret NIH guidelines for working with pathogens, Tracy said. Although UW-Madison disagreed with the NIH's finding that Kawaoka's work should be done in a BSL-4 lab, it quickly complied, he said. On Oct 28, 2006, the university halted work with the Ebola material, and Kawaoka sent the projects to a BSL-4 lab in Winnipeg, Man., where he has continued to be involved with the work.

Federal officials are in a difficult position, Tracy said, because it appears that different federal agencies have different biosecurity standards.

Hammond and his group are playing up inconsistencies among the government agencies to suggest that biological work is being done improperly, the public is at risk, and federal oversight is lax, Tracy said. "And I disagree," he added.

CDC official downplays risk
The National Institute of Allergy and Infectious Diseases, part of the NIH, did not respond to a CIDRAP News request for comment on the Sunshine Project report. But Rob Weyant, director of the CDC's Select Agent Program, told CIDRAP News that the CDC doesn't regulate nucleic acids of the Ebola virus, which is apparently what Kawaoka's lab was working with. "Ebola is one of the most dangerous microbes, but when you break it up and take out the nucleic acids, the nucleic acids themselves are much less hazardous," he said.

Changing cDNA from the Ebola virus into its infectious RNA form is possible, but not easy, Weyant said. When CDC inspectors toured Kawaoka's lab they would have made sure good safety procedures were in place for work with cDNA material of the Ebola virus, he added.

At the CDC, researchers do work with Ebola nucleic acids outside BSL-4 labs, Weyant said. "This is based on a risk assessment and a pretty good understanding of these viruses," he said, adding that it was "unclear" if the agency's researchers work with the material in BSL-2 labs.

Congress to look into lab safety
The apparent rule violations at the UW-Madison lab follow a string of other violations at four Texas universities that also were exposed recently by the Sunshine Project. In late June the CDC ordered a biodefense research laboratory at Texas A&M University to stop all work on select agents and toxins while the agency investigated reports of lab workers infected with the category B bioterrorism agents Brucella and Coxiella burnetti. A week ago the Sunshine Project revealed that three University of Texas facilities recently had lab accidents with dangerous pathogens, including the agents of anthrax, tularemia, and shigellosis.

Concerns about safety at US biodefense labs come amid ongoing foot-and-outh (FMD) disease outbreaks in the United Kingdom that health officials say were linked to release of the virus from flooded drain pipes at a facility in Pirbright that houses an FMD vaccine producer and a government research institute.

Safety breaches at US biodefense labs have also caught the attention of lawmakers. The US House Committee on Energy and Commerce announced it would hold a hearing on Oct 4 to explore the risks associated with the rising number of BSL-3 and BSL-4 labs in the United States, according to a Sep 21 news release from the committee.

Rep John Dingell, D-Mich., chairman of the committee, said construction of biodefense labs has surged over the past several years, funded in part by the federal government.

"Yet, little information is available about the number of labs being operated in the US and whether they are safely run," he said. "While the research conducted at these labs is certainly valuable, we must make sure that it does not pose a risk to the public health."

See also:

Sep 19 CIDRAP News story "Biosafety lapses reported at 3 more Texas labs"

Sep 5 CIDRAP News story "CDC details problems at Texas A&M biodefense lab"

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