Lax Lab Safety

Recent incidents of mishandling anthrax and bird flu samples at government labs have raised concerns about what safety violations are occurring at other high-containment laboratories.

Troubling breaches of protocol. Gaps in review systems. Errors in judgment. Next to "widespread exposure," these are the last phrases anyone wants to hear in a discussion of government laboratories that handle dangerous pathogens. But that's exactly what was described during a government oversight hearing on biosafety lapses at Centers for Disease Control and Prevention (CDC) facilities. "These incidents should never have happened, and the lack of adequate procedures and oversight that allowed them to happen was totally unacceptable," testified a contrite Thomas R. Frieden, director of the CDC, in July.

Frieden appeared before the House Subcommittee on Oversight and Investigations to answer for the recent lapses in protocol that led to inappropriate exposure of an active anthrax sample and cross-contamination of a contagious strain of H5N1 bird flu.

"The incident revealed concerns about the use of inappropriate protocols and lack of adherence to procedure, and points to needed improvements in our oversight systems," Frieden said, regarding the anthrax case. Although he was only referring to problems in the CDC's facilities, the incidents are an example of the extreme lack of oversight by the government of public and private high-containment laboratories across the country, according to the U.S. Government Accountability Office (GAO).

The biosafety lapses resulted in a July GAO report on the need for a set of national standards for laboratories that handle dangerous pathogens and emerging infectious diseases. Nancy Kingsbury, Ph.D., managing director of applied research and methods at GAO, appeared before the same subcommittee and pointed out that the CDC isn't the only agency with laboratories that need more oversight.

"No executive or legislative mandate directs any federal agency to track the expansion of all high-containment laboratories," Kingsbury told the legislators. Although laboratories that handle select agents must register with government agencies, there are other laboratories that handle potentially dangerous pathogens, including certain strains of the Ebola virus, that do not have to register with the government. And information about these facilities—the number, location, and type of pathogens they handle—is unknown.

Incidents. The CDC handles anthrax bacteria for testing purposes and to improve prevention and treatment options. In June of this year, a CDC bioterrorism lab in Atlanta was conducting research with a sample of active, infectious anthrax bacteria and sought to render it into an inactive form, according to Frieden.

Believing that the entire live anthrax sample had been killed, CDC staff transferred samples to two other labs with lower safety and security protocols. However, eight days after the transfer, scientists at the original laboratory observed unexpected growth in the purportedly inactive samples, which raised concerns that the samples passed on may have been active as well. The CDC identified everyone who may have come in contact with the samples and ultimately recommended that 81 staff members start taking antibiotics. The samples were collected and transferred back to the higher-security lab, and fortunately no employees have shown signs of infection.

Although Frieden told legislators that "there was at most a very small chance that anyone was exposed to live anthrax during this incident," later reviews found that there had been multiple violations and breaches of protocol that led to the potential exposure. Concerns were also raised about the lack of communication and rapid response following the incident. "We focused on managing the situation with at-risk staff without making information more widely available to others in the CDC community," Frieden said at the hearing.

During the subsequent investigation of CDC biosafety lapses, it was discovered that in March of this year a culture of nonpathogenic avian influenza—bird flu—was cross-contaminated with the highly contagious H5N1 strain and shipped to another facility. The contamination was discovered two months later, and the CDC laboratory was informed, but other necessary notifications were neglected, Frieden noted. "The larger context of these other incidents reinforces and amplifies that strong, rapid, and comprehensive action is needed," he said.

Richard H. Ebright, a professor at Rutgers University and laboratory director at Waksman Institute of Microbiology, put it bluntly: "The 2014 CDC anthrax incident involved multiple violations of biosafety and biosecurity recommendations in each of three CDC laboratories—at least seven distinct violations in total." Ebright also spoke at the hearing on the biosafety incidents and said that they raise both safety and security concerns and are not isolated events. He also pointed out that U.S. Department of Health and Human Services audits reported "substantive violations," including failures to ensure physical security, restrict access, and document inventories. Training records for one out of every three employees were unverifiable, and unauthorized transfers of select agents to other laboratories or individuals were also reported. What's worse, Ebright said, is that the audits show no evidence of improvement over time.

Frieden outlined to lawmakers the changes being made at CDC laboratories, including reviewing and updating select agent handling procedures, initiating an incident command structure early in the response to an incident, and establishing a working group of experts to suggest improvements in laboratory safety.

Implications. There are two types of high-containment laboratories in the United States: those that are federally registered with the National Select Agent Registry and those that aren't. GAO's Kingsbury tells Security Management that facilities handling certain pathogens that could pose a severe threat to human, animal, or plant health must register with either the CDC's Division of Select Agents and Toxins or the U.S. Department of Agriculture's (USDA) Animal and Plant Health Inspection Service.

There are more than a thousand of these select agent laboratories, which operate across government, academic, and private sectors. These registered facilities are required to report any irregular episodes, such as the anthrax and bird flu incidents.

Much less is known about high-containment laboratories that do not deal with select agents. These facilities are run by a range of organizations, from federal agencies to academic researchers to pharmaceutical companies. And since these laboratories don't handle select agents, they do not need to register with the CDC or USDA. As far as Kingsbury knows, there is no comprehensive list of how many of these facilities there are or what pathogens they work with.

And just because they don't handle select agents doesn't mean they don't work with dangerous pathogens, Kingsbury notes. For example, agents such as tuberculosis and certain strains of bird flu and Ebola are not covered by the select agent program—and there are a number of pharmaceutical companies working with these diseases to create vaccines, she says. "There needs to be better knowledge about how many laboratories have been built and who oversees them." 

Kingsbury is quick to point out that the microbiology community is extraordinarily safety-conscious, and the number of incidents compared to the number of laboratories needs to be kept in perspective. Although there have been disturbing lapses, none of them evolved into biological disasters, like the Ebola epidemic in West Africa. "That has not happened, which I think is a compliment to the whole community of microbiologists," she says.

However, the recent incidents are just another reminder that something needs to be done about laboratory oversight.

The GAO wants to develop a national strategy that would not only keep track of both registered and unregistered laboratories, but also help them develop a strategic view for facing security and biological threats both now and in the future. Kingsbury said that the GAO has been pushing this agenda for seven years—ever since a foot-and-mouth disease outbreak decimated the livestock industry in the United Kingdom.

In August 2007, after livestock tested positive for foot-and-mouth—a highly contagious virus that affects certain animals—investigators traced the source of the outbreak to a government animal health laboratory where a burst pipe leaked the virus. The outbreak lasted almost a month and caused a $3 billion agricultural disaster in southern England. The outbreak illustrated the importance of laboratory maintenance, which is especially relevant in the United States due to the large increase in high-containment laboratories over the past decade, according to Kingsbury.

"After the anthrax attacks in 2001, seven or eight different agencies started throwing money at these issues and started building laboratories," she explains. "They all did it within their own mission spaces, and they all did it with congressional support."

Meanwhile, though, budgets have been slashed but the laboratories haven't shut their doors—in fact, the number of facilities has continued to increase. "Frankly, what has worried us since 2007 has been whether, having built all these laboratories, there will be sufficient funding going forward to maintain them," Kingsbury says.

At the Oversight and Inspections hearing, Ebright testified that between 2008 and 2010, an additional 133 high-containment laboratories entered the field—and that's just the number of registered facilities. In his witness testimony, Ebright suggested that the number of select-agent laboratories be "sharply reduced" to fewer than 50.

In the meantime, there are more than 1,500 registered and an unknown number of unregistered high-containment laboratories.  Kingsbury says that without oversight, the government can't gain a big-picture view of what's happening with these facilities. "Right now it's not clear to us, because we haven't done a systematic study of all the laboratories and all the budgets, whether these laboratories are going to be able to be maintained going forward at the level they really need be," she says.

The GAO's 2013 study urged that the U.S. Office of Science and Technology Policy (OSTP) "ensure that periodic assessments of national biodefense research and development needs are conducted." Kingsbury says that "at a high level," OSTP agreed that there was a need for a national strategy, but leaders couldn't find a viable solution to get agencies to work together to create standards. "Their idea was an interagency working group, which in the history of the government doesn't actually make decisions very effectively," Kingsbury notes.

The last solution at this point is legislation, Kingsbury says. But that's easier said than done. Although individual agencies and organizations have put together standards for their laboratories—such as the CDC's response to the recent lapses—they aren't industrywide solutions. Funding is another concern. "In this budget environment, setting up a new agency to do that is a probability close to zero," Kingsbury says.

However, the GAO is garnering support from industry associations, such as the American Biological Safety Association, and individual agencies and organizations. It is also looking into existing standards, from a report by the U.S. Department of Energy on managing its laboratories to the Nuclear Regulatory Commission's regulations, for examples on how to form a strategy for high-containment laboratories.