Genomic analysis identified the 1995 virus as identical to a 1963 isolate, with no indication it had been circulating for 28 years. It was another case of frozen evolution, but unlike the vaccine-related VEE outbreaks, the 1963 virus had never been used in a vaccine. Suspicion fell on an inadvertent release from a virology lab, either by an unrecognized infection of a lab worker or visitor, or escape of an infected laboratory animal or mosquito. The major scientific group working on VEE published a paper in 2001 stating the 1995 outbreak most likely was a laboratory escape, with considerable circumstantial evidence: The outbreak strain was isolated from an incompletely inactivated antigen preparation used on the open bench in the VEE laboratory located at the outbreak epicenter. But clear proof was lacking, and the group subsequently said it was reconsidering this conclusion.
SARS outbreaks after the epidemic. The 2003 Severe Acute Respiratory Syndrome outbreak spread to 29 countries, causing more than 8,000 infections and at least 774 deaths. Because 21 percent of cases involved hospital workers, it had the potential to shut down health care services wherever it struck. It is particularly dangerous to handle in the laboratory because there is no vaccine, and it can be transmitted via aerosols.
Moreover, about 5 percent of SARS patients are “super-spreaders” who infect eight or more secondary cases. For instance, one patient spread SARS directly to 33 others (reflecting an infection rate of 45 percent) during a hospitalization, ultimately leading to the infection of 77 people, including three secondary super-spreaders. A super-spreader could turn even a single laboratory infection into a potential pandemic.
SARS has not re-emerged naturally, but there have been six escapes from virology labs: one each in Singapore and Taiwan, and four separate escapes at the same laboratory in Beijing.
The first was in Singapore in August 2003, in a virology graduate student at the National University of Singapore. He had not worked directly with SARS, but it was present in the laboratory where he worked. He recovered and produced no secondary cases. The World Health Organization formed an expert committee to revise SARS biosafety guidelines.
The second escape was in Taiwan in December 2003, when a SARS research scientist fell ill on a return flight after attending a medical meeting in Singapore. His 74 contacts in Singapore were quarantined, but again, fortunately, none developed SARS. Investigation revealed the scientist had handled leaking biohazard waste without gloves, a mask, or a gown. Ironically, the WHO expert committee called for augmented biosafety in SARS laboratories the day after this case was reported.
In April 2004, China reported a case of SARS in a nurse who had cared for a researcher at the Chinese National Institute of Virology. While ill, the researcher had traveled twice by train from Beijing to Anhui province, where she was nursed by her mother, a physician, who fell ill and died. The nurse in turn infected five third-generation cases, causing no deaths.
Subsequent investigation uncovered three unrelated laboratory infections in different researchers at the NIV. At least of two primary patients had never worked with live SARS virus. Many shortcomings in biosecurity were found at the NIV, and the specific cause of the outbreak was traced to an inadequately inactivated preparation of SARS virus that was used in general (that is, not biosecure) laboratory areas, including one where the primary cases worked. It had not been tested to confirm its safety after inactivation, as it should have been.
Foot-and-mouth disease in the U.K. in 2007. Foot-and-mouth disease infects cloven-hoofed animals such as pigs, sheep, and cattle. It has been eradicated in North America and most of Europe. It is highly transmissible, capable of spreading through direct contact on the boots of farm workers and by natural aerosol that can spread up to 250 kilometers. Outbreaks in FMD-free areas cause economic disaster because meat exports cease and animals are massively culled. A 2001 U.K. outbreak resulted in 10 million animals killed and $16 billion in economic losses.
In 2007, FMD appeared again in Britain, 4 kilometers from a biosafety level 4 laboratory—a designation indicating the highest level of lab security—located at Pirbright. The strain had caused a 1967 outbreak in the United Kingdom but was not then circulating in animals anywhere. It was, however, used in vaccine manufacture at the Pirbright facility. Investigations concluded that construction vehicles had carried mud contaminated with FMD from a defective wastewater line at Pirbright to the first farm. That outbreak identified 278 infected animals and required 1,578 animals to be culled. It disrupted U.K. agricultural production and exports and cost an estimated 200 million pounds.
Federal law bans FMD virus from the continental United States, and it is held only at the U.S. Department of Agriculture Plum Island facility off Long Island, N.Y. Currently, however, its replacement, the National Bio and Agro-Defense Facility, is under construction in Manhattan, Kan., under the aegis of the Department of Homeland Security. Moving FMD research to the agricultural heartland of the United States was opposed by many groups, including the Government Accountability Office, but Homeland Security decided on the Kansas location. In upgrading facilities to counter the threat of agro-bioterrorism, the department is increasing the risk to U.S. agriculture of unintentional release.
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These narratives of escaped pathogens have common themes. There are unrecognized technical flaws in standard biocontainment, as demonstrated in the U.K. smallpox and FMD cases. Inadequately inactivated preparations of dangerous pathogens are handled in laboratory areas with reduced biosecurity levels, as demonstrated in the SARS and VEE escapes. The first infection, or index case, happens in a person not working directly with the pathogen that infects him or her, as in the smallpox and SARS escapes. Poor training of personnel and slack oversight of laboratory procedures negate policy efforts by national and international bodies to achieve biosecurity, as shown in the SARS and smallpox escapes.
It is hardly reassuring that, despite stepwise technical improvements in containment facilities and increased policy demands for rigorous biosecurity procedures in the handling of dangerous pathogens, potentially high-consequence breaches of biocontainment occur nearly daily: In 2010, 244 unintended releases of bioweapon candidate “select agents” were reported.
Looking at the problem pragmatically, the question is not if such escapes will result in a major civilian outbreak, but rather what the pathogen will be and how such an escape may be contained, if indeed it can be contained at all.
Experiments that augment virulence and transmissibility of dangerous pathogens have been funded and performed, notably with the H5N1 avian influenza virus. The advisability of performing such experiments at all—particularly in laboratories placed at universities in heavily populated urban areas, where potentially exposed laboratory personnel are in daily contact with a multitude of susceptible and unaware citizens—is clearly in question.
If such manipulations should be allowed, it would seem prudent to conduct them in isolated laboratories where personnel are sequestered from the general public and must undergo a period of exit quarantine before re-entering civilian life. The historical record tells us it is not a matter of if but when ignoring such measures will cost health and even lives. Perhaps many lives.
A version of this essay originally appeared in the Bulletin of the Atomic Scientists. It summarizes a more detailed review of the historical record with appropriate scientific references; it is available on the website of the Center for Arms Control and Non-Proliferation.