BY STEVE SMITH
BOSTON, Mass.-City of Boston and Boston University officials are determined to improve monitoring of research taking place at the university’s biosafety labs, in the wake of a contamination incident last spring that infected three researchers.
The researchers became ill after being exposed to the potentially lethal bacterium known as tularemia. Although it remains unclear exactly how the researchers became infected, or the source of the contamination, Boston University officials acknowledged that the researchers had violated safety procedures while in the Biosafety Level (BSL) 2 lab.
Biosafety labs are credited and audited by the Centers for Disease Control (CDC; www.cdc.gov), and are categorized according to the level of hazard involved in the research. A BSL-1 lab, for example, is used for researching those agents that are considered safe when in contact with healthy humans, while a BSL-2 lab, like the one at Boston University, is designated for work with agents that have a moderate potential of being hazardous to human health. A BSL-3 lab designation means agents have the potential to cause fatal disease, while a BSL-4 lab is reserved for agents of highest risk to public health, such as anthrax and plague.
A basic requirement of research in a BSL-2 lab is that agents be handled within a vented hood-an enclosed box with air filtration technology. It is believed that the BU researchers at times worked with tularemia samples outside of the hoods because the boxes reportedly contained other materials that interfered with the research.
Compounding the contamination incident is the uncertainty of how a normally benign strain of the “rabbit fever” agent became infectious, and where it came from.
Even as Boston University pursues construction of one the nation’s few BSL-4 labs-and one of only two sites in the country designated by the National Institute of Allergy and Infectious Disease for the study of deadly bioterrorism pathogens, such as anthrax-the city’s Public Health Commission and university officials are promising stricter oversight on research labs. The Commission, in fact, wants to hire an inspector to make surprise visits to research labs-both public and private-to ensure that safety procedures are followed.
Although more thorough adherence to security procedures and laboratory safety guidelines may be the best ways to prevent further incidents in BSL-2 labs, some in the academic research community acknowledge that it’s easier said than done.
“There’s a whole host of overlapping oversight for research risk management here, but we’re constantly aware that a problem can materialize in the future-complacency is the biggest enemy,” says Earle Holland, executive director of research communications at Ohio State University’s College of Biological Sciences (OSUCBS) in Columbus.
Ohio State currently operates two BSL-3 labs both on and off campus, with a third facility being built on the west campus that will contain up to seven BSL-3 labs in one unit.
While Boston University is convinced that what happened in its BSL-2 lab would not happen in the pending BSL-4 lab where safeguards are most strict, Holland cautions that nothing should be left to chance. “There’s nothing different about a BSL-2, -3 or -4 in the sense of how secure they should be. Physical or process safeguards are essential for all levels.”
The problem with maintaining safety procedures in a BSL-2 lab, however, is that it is often unmonitored while a BSL-3 and especially Level 4 lab would see university or private-sector officials personally monitoring activities, procedures, and security.
“I’m a bit worried about researchers working in this gray area of BSL-2 where so much is based on trust of [agent] sources,” says Dr. Cecil Smith, assistant vice president of environmental health and safety at OSUCBS. “Typically, in a BSL-2 lab, investigators verify that the materials received are what they ordered. It sounds like a simple process, but it often becomes, ‘Well, I got it from my colleague’,” says Smith. “There’s a trust factor [because of the low-risk level of the agents involved] that what you’re getting is OK.”
Smith and Holland observe that the CDC maintains strict criteria for handling of select agents, which are microorganisms or infectious substances capable of causing death, disease or other hazards among the public. At Ohio State, numerous procedures are in place to prevent mishaps with select agents. “All faculty who wish to conduct research here must go through SOPs for each lab,” says Holland. “We have a sit-down conversation so that we’re comfortable with the person working in a facility.”
Specifically, Holland says, researchers must work in pairs, and use of select agents requires passing federal security background checks. A campus biosafety committee is also in place to help assure safety.
Smith adds, “Biosecurity at Ohio State is very tight-we want to know who’s doing it, and how they are controlling work in the lab.” In a university setting, he says, it’s not uncommon to have buildings containing both classroom and lab space that are open to people coming and going. Security measures “do present a challenge in that situation, and much diligence is needed,” says Smith.
Part of the preventative measures at Ohio State include educational awareness programs about select agents, materials, how they’re stored and handled, and who and how many people might be coming and going through a particular lab facility at any time.
“With all of the steps,” adds OSUCBS’ Holland, “it’s not uncommon for researchers to perceive these as obstacles standing in their way. They just want to get to their research. But we’ve got to get them to buy into it. It’s an ongoing challenge.”
In the Boston University incident, the mystery of how the agent became contaminated in the first place is what concerns others in the academic research community. The BU researchers believed that they were receiving a harmless strain of the tularemia agent from the University of Nebraska at Lincoln; in fact, The Boston Globe reports that scientists at the University of Nebraska had never worked with a lethal strain of tularemia. Investigators ruled out the possibility that researchers had somehow mixed a benign strain with a lethal one. Yet somehow, contamination got into the supply.
“At that [BSL-2] level of research, you trust that what you get is OK,” says Smith. “At most universities, there’s not some overriding policy that says you need to verify what you receive.” But Smith observes that the Boston University incident has “sent a clear message to the research community. You can’t take it [the samples received] at face value. You need to validate on the shipping end as well as the receiving end.”
Ohio State officials agree with Dr. Thomas Moore, acting provost of Boston University’s medical campus, who while confident that such an incident would not be repeated in a BSL-4 lab, says it has “heightened our awareness and attentiveness to safety issues in labs that operate at a lower level of security.”
In the BU case, the controversy was further heightened because of a decision by city officials not to disclose the incident to the public since there was no risk to public health. “The public perception of safety issues is always difficult to deal with,” admits Smith. “There are too many TV shows that give the wrong perceptions of safety and things that cause incidents.”
“The university arena, ultimately,” says Smith, “remains a safe place to conduct biological research,” but he adds that BSL-2 contamination can be minimized further by continuing education for both the public and those who use the research facilities.