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Biodefense 'gold rush' raising concerns as labs rapidly increase
'It would be a damn shame if somebody died out of ignorance.'
A rapid, ongoing expansion in the number of high-containment biodefense laboratories throughout the nation is raising serious questions about the safety of lab workers, the risk to the public, and the lack of government oversight to prevent accidents and security breaches.
The increase in the number of biosafety level (BSL)-3 and BSL-4 labs is raising a host of issues, from adequate training of an expanding work force to the release of dangerous pathogens via accident of subterfuge. Driven by unprecedented federal investment in biodefense research, the lab expansion is taking place at the private, academic, state, and federal levels throughout the country.
"This is kind of like a gold rush," says Alan Pearson, PhD, director of the biological and chemical weapons control program at the Center for Arms Control and Non-Proliferation in Washington, DC. "You have multiple agencies who want to have a piece of this. You have multiple institutions that are looking for funding, who see these high-containment labs as a marker that they are a cutting-edge research facility."
The expansion exacerbates problems in a fragmented national biosafety and biosecurity system that already is dogged by systemic weaknesses, he says. "If you have a large expansion in facilities and the number of people working on dangerous pathogens — but you're not doing anything to strengthen what was already a weak oversight system — then your risk increases," Pearson tells Bioterrorism Watch. "If you're going to have expansion [of labs] you need to have a corresponding increase in your ability to mitigate the potential risk associated with that expansion."
The criticism and concern is not just coming from nonproliferation advocates and consumer watchdog groups. The Government Accountability Office (GAO) reports to Congress that "the expansion of BSL-3 and BSL-4 labs taking place in the United States is proceeding in a decentralized fashion, without specific requirements as to the number, location, activity, and ownership of such labs. While some expansion may be justified to address deficiencies in lab capacity for the development of medical countermeasures, unwarranted expansion without adequate oversight is proliferation, not expansion. Since the full extent of the expansion is not known, it is unclear how the federal government can ensure that sufficient but not superfluous capacity — that brings with it additional, unnecessary risk — is being created."1
According to the GAO report, there were five BSL-4 labs that handle the most dangerous agents (e.g., Marburg and Ebola viruses) in the United States prior to 9/11 and the anthrax aftermath. Currently there are 14 BSL-4 labs and another in the planning stages. These labs work with agents that are likely to cause serious or lethal human disease for which preventive or therapeutic interventions usually are not available (e.g., high individual risk and high community risk).
Information on expansion is available about BSL-4 high-containment labs that are registered with the Centers for Disease Control and Prevention (CDC) and the U.S. Department of Agriculture's (USDA) Select Agent Program, the GAO noted. "However, much less is known about the expansion of labs outside the Select Agent Program, as well as the nonfederally funded labs, including location, activities, and ownership," the GAO report states. (See map.) "No single federal agency, according to 12 agencies' responses to our survey, has the mission to track the overall number of BSL-3 and BSL-4 labs in the United States. Though several agencies have a need to know, no one agency knows the number and location of these labs in the United States. Consequently, no agency is responsible for determining the risks associated with the proliferation of these labs."
The untracked expansion is primarily occurring with BSL-3 labs. Though a step down from level four in terms of risk to staff and the surrounding environment, these labs work with agents that are associated with serious or lethal human disease for which preventive or therapeutic interventions may be available (e.g., high individual risk but low community risk). Examples include: plague, tularemia, tuberculosis, hantaviruses, HIV. Moreover, BSL-3 labs can be at clinical, diagnostic, teaching, research, or production facilities. According to the CDC, laboratory personnel should have specific training in handling pathogenic and potentially lethal agents, and must be supervised by competent scientists who are experienced in working with these agents.
"It is not exactly clear how many level three labs there are," says Gigi Gronvall, PhD, senior associate at the Center for Biosecurity of University of Pittsburgh Medical College. "The government should know, but part of that is just how they are classified. Some hospitals have them and they are not even primarily bioterrorism-focused. A lot of diseases — TB for example — tend to be worked on in Level 3. [We] do know how many laboratories have signed up to work with the so-called select agents — those considered potential weapons. If they don't register, they are breaking the law."
Though emphasizing the need for biosecurity research, Gronvall says the government has done a poor job of explaining why it needs so many labs, which are designed in part to develop medical countermeasures to bioweapons targeted at humans and agriculture. "The federal government needs to do a better job of justifying why these labs are needed so they can explain it to the public and get their support," she says. "I can tell you that these labs are necessary in order to study certain diseases that can't be worked on in any other way."
Such research and animal testing is necessary because most of the disease being researched arise relatively infrequently in nature. "These diseases aren't very common in the world so you can't follow natural infections and outbreaks," she says. "There is a [need] for more animal testing. These labs provide a safe environment for that, but I think there should be more control over how these laboratories are managed."
The nation has gone from a consensus in the 1990s that there was too little high-containment lab space, to an open question of whether we are now exceeding the research capacity that is needed. "It is a debatable point whether we have the right amount of [lab] space, too much or too little," she says. "It's not clear, and this is what the federal government should explain."
While the threat to the public has been emphasized by opponents of the labs, Gronvall sees the expansion as a particular threat to the thousands of laboratory workers manning these sites. "It used to be there were just a couple of these labs in the country and there was a very small, tight-knit group of people working on this," she says. "It's different when you scale up like this. The things that used to work — the sort of intense mentor training — need to be more formalized when you start scaling up."
Indeed, though it dealt with clinical labs rather than biodefense labs, a recent government exercise revealed lab workers using outmoded and dangerous practices even when alerted that the specimen in the drill should be considered a bioterrorism agent.
"Of course, I have concerns for the public, but the people who are going to be most in danger are the workers," she says. "I think we need to ensure that they are safe. It would be a damn shame if somebody died out of ignorance. If they are not trained correctly they run the risk of getting infected. These are not diseases you want to be infected with."
The Texas A&M incident
In reporting the expansion, the GAO cited three incidents of concern: a temporary power outage at the CDC's new BSL-4 lab in Atlanta, release of foot-and-mouth disease virus at Pirbright in the United Kingdom, and failure to report to CDC exposures to select agents by Texas A&M University (TAMU) in College Station. In the Texas A&M incident, a lab worker was infected with Brucella in 2006. Brucellosis is a bacterial zoonotic infection usually dangerous enough to be listed among CDC's Category B bioterrorism agents.
While the TAMU incident underscores both the risk to workers and the lack of adequate oversight, it also suggests that institutions may have disincentives to thoroughly investigate and openly report incidents in these labs. According to the GAO, at the time of the exposure on Feb. 9, 2006, the lab worker did not know she was infected nor did anyone else in the lab. In fact, the CDC conducted a routine inspection of TAMU on Feb. 22 — 13 days after the exposure—but had no way of knowing that it had happened.
According to the exposed worker, it was more than six weeks after the exposure that she first fell ill. Then, the first consultation with her physician indicated that she had the flu. It only was after the symptoms persisted that a consultation with an infectious disease specialist confirmed that her blood contained an unknown microorganism, the GAO reported.
If the worker had not recalled the experiment with Brucella and alerted her physician, she might have developed an even more severe infection. Fortunately, the disease is not easily transmitted between humans and there was no risk of spread to the surrounding community. That cannot be said for all diseases worked on in such labs, including SARS and tuberculosis. Since clinical symptoms can take weeks to become apparent for some agents, infected workers could be the index case for an outbreak in the community, the GAO emphasized. In addition to the incident of exposure to Brucella, the CDC noted several incidents of potential exposure to Coxiella burnetii that TAMU had failed to report. "The inherent weaknesses of an oversight system based on self-policing are highlighted by the Texas A&M University case," the GAO concluded.
"While CDC inspected the labs at Texas A&M in April 2006, as part of its routine inspection, its inspectors failed to identify that a worker became exposed and ill; unauthorized experiments were being conducted and unauthorized individuals were entering the labs; and agents and infected animals were missing."
Indeed, it was not until a public advocacy group — the Sunshine Project — found out about the Brucella incident that TAMU reported it to the CDC, the GAO reported. The incident raises serious concerns about how well the CDC polices select agent research being conducted in more than 400 high-containment labs at various universities around the country, the GAO emphasized. "If similar safety breaches are occurring at other labs, they are not being reported," said Keith Rhodes, chief technologist in the Center for Technology and Engineering Applied Research and Methods, who delivered the GAO report in testimony before Congress. "And the CDC is not finding them either. According to the experts, no one knows whether the Texas A&M incidents are the tip of the iceberg or the iceberg."
The GAO reports that the key overall challenges on the lab expansion issue include: