Given the rapid increase in the number of laboratories around the world that do research on diseases of bioterrorism concern, such as anthrax and plague, and emerging infections, such as SARS and avian influenza, there is an urgent need to prevent pathogenic microbes from escaping accidentally from a lab or being stolen by terrorists and criminals. With a few exceptions, dangerous bacteria and viruses can be isolated from nature, but different strains tend to vary widely in virulence, or the ability to cause illness and death. For this reason, would-be bioterrorists would be more likely to steal well-characterized "hot" strains from a research laboratory or culture collection.
Despite the risks of laboratory accidents and deliberate misuse, a global regime for the safe and secure storage and handling of dangerous pathogens is currently lacking. Dozens of laboratories in countries like China, India, Indonesia, Malaysia, and Pakistan do research on epidemic diseases without effective regulatory structures. In principle, all such facilities should be required to register with national authorities and implement minimum requirements for the inventory, physical protection, access control, and tracking of pathogen stocks. In addition, scientists and technicians seeking to work with hazardous biomaterials should undergo a vetting process to verify their scientific bona fides and make sure that they are not affiliated with a terrorist organization. Although creating such a global infrastructure for pathogen safety and security will be a major challenge, a potential vehicle already exists: the ongoing effort to safeguard all laboratory samples of poliovirus after the disease has been eradicated from nature.
Polio eradication campaign
For the past two decades, the World Health Organization (WHO), the United Nations Children's Fund (UNICEF), and the Rotary Foundation have pursued a worldwide vaccination campaign to eradicate polio, a viral disease that attacks the nervous system and causes paralysis, mainly in young children. Launched in 1988, the Global Polio Eradication Initiative has since become the largest international public health effort ever undertaken, with an investment of more than $5 billion and the vaccination of billions of children. To date, the polio eradication campaign has reduced the incidence of the disease by about 99 percent, from an estimated 350,000 cases worldwide in 1988 to only 1,315 in 2007. Although in recent years the initiative has suffered setbacks in Nigeria, India, and elsewhere, WHO still intends to finish the job. At the organization's annual meeting in May 2008, Director-General Margaret Chan declared that polio eradication is now WHO's "top operational priority."
After the transmission of wild poliovirus has been completely interrupted, careful surveillance for new outbreaks will continue for at least three years before the world can be certified as polio-free. At the same time, WHO will strive to minimize the risk that the disease could re-emerge because of the accidental release of poliovirus from a laboratory. At present, thousands of facilities worldwide hold materials containing infectious or potentially infectious poliovirus, including reference strains, clinical specimens from polio patients, and water and sewage samples collected from areas where the disease was endemic. Poliovirus could potentially spread outside the laboratory through effluents discharged into sewage, solid wastes transported to landfills, spent air released into the atmosphere, or the contamination of workers' skin or clothing.
The history of smallpox eradication offers some cautionary lessons. Less than a year after a global vaccination campaign under WHO auspices contained the last natural outbreak in 1977, two cases of smallpox resulted from an accident in a research laboratory at the University of Birmingham in England. A medical photographer who worked directly above the smallpox lab became infected with the virus, apparently because of a leak in the building's ventilation system. Before dying of smallpox, the photographer infected her mother, who survived. But the lab director, overcome with remorse over the incident, took his own life. In response to this tragedy, WHO urged all member countries either to destroy their stocks of smallpox virus or transfer them to an authorized repository. As a result, the number of facilities worldwide with declared stocks of the smallpox virus declined from seventy-five in 1975 to only two (in the United States and Russia) a decade later.
In addition to the accidental release of poliovirus from a laboratory, some experts worry about its deliberate use as a terrorist weapon. Although polio is nowhere near as lethal as smallpox, a bioterrorist incident that produced even a few cases of infantile paralysis in a major city would spark widespread terror. Accordingly, the destruction of most laboratory specimens of poliovirus, and the effective containment of those that remain, will help to minimize the risk that the disease could return through an accident or a malicious attack.
Containment of wild polioviruses
To ensure the secure storage and handling of infectious materials containing poliovirus after the disease has been eradicated, WHO has developed a Global Action Plan for Laboratory Containment of Wild Polioviruses, which was first published in 1999 and revised in 2004 and 2008. The implementation of this plan involves four phases, which are tied to the progress of the eradication campaign. During the pre-eradication period, countries must survey all biomedical facilities on their territory and inventory those holding wild poliovirus and potentially infectious materials. By the end of 2006, a total of 152 countries had surveyed more than 200,000 research labs, clinical labs, and vaccine plants and identified roughly 850 housing relevant materials.
The next step is for countries to establish national goals and policies for the post-eradication era, along with enforceable legislation and regulations for the laboratory containment of wild polioviruses. Each government must advise facilities holding samples of the virus to decide whether to retain their stocks and upgrade their level of biocontainment and security, transfer their specimens to a better-equipped reference laboratory, or destroy them. The latest version of the Global Action Plan aims to minimize the risk of an accidental release by reducing the number of facilities that retain stocks of live poliovirus to about 20 worldwide, the number considered necessary for vaccine manufacture, diagnostic work, and basic research. The Global Action Plan also calls for the development of international standards for the siting, safety, and security of the authorized repositories, as well as oversight and inspection measures at both the national and international levels.
A global pathogens initiative
The Global Action Plan for Laboratory Containment of Wild Polioviruses offers a valuable opportunity to ensure the safe and secure storage and handling of all infectious-disease agents that pose significant risks to public health. Polio eradication offers a good platform for such a comprehensive initiative because specimens containing poliovirus are far more widely dispersed than was the case with smallpox virus. Now that the Global Action Plan is requiring WHO member countries to survey their biomedical facilities and identify those that possess poliovirus, it would not demand a great deal more effort to do the same for the full range of dangerous pathogens.
With the approval of its member states, WHO could piggyback this broader effort on the poliovirus containment plan. A resolution by the World Health Assembly (the annual policy making body of the 193 member states of WHO) establishing a Global Pathogens Initiative could require countries to establish a list of "high-consequence pathogens," or infectious agents and toxins that pose particular risks for public health and national security. This list would be tailored to the infectious-disease situation in each country and would be readily modifiable in response to newly emerging infections and scientific advances. WHO member governments would then implement a set of safety and security rules for public and private facilities that store and handle listed agents. Ideally, this regime would go beyond the traditional "guns, gates, and guards" approach to address the full range of outsider and insider threats.
WHO has already developed a widely used Laboratory Biosafety Manual and, more recently, a complementary set of laboratory security guidelines titled Biorisk Management: Laboratory Biosecurity Guidance. Drawing on these two manuals, WHO member states could require all laboratories and culture collections that possess high-consequence pathogens to register with the national government, inventory their stocks, conduct a facility risk assessment, adopt measures for physical security and access control, screen lab personnel who are granted access to listed agents, monitor use and report all transfers, and prepare emergency plans in the event of an accidental release or a breach in security. To oversee and enforce the regime, national governments would conduct periodic on-site inspections and impose fines and other sanctions for the unregistered possession of listed agents or a failure to comply with the rules.
In order to attract international support, a Global Pathogens Initiative should not focus exclusively on the security dimension. Instead, it should be framed in broader public-health terms as a means to protect communities living near infectious-disease labs from accidental releases of deadly disease agents, as well as theft or diversion by criminals or terrorists, and to shield the scientific enterprise from the political backlash that would result. Wealthy countries could support the initiative by offering financial and technical assistance to poorer countries that wish to participate and by making voluntary contributions for this purpose outside the regular budget of WHO, which is chronically underfunded. Expanding the containment of wild poliovirus to cover all high-consequence pathogens would be a major step forward toward a global regime for managing biorisks that significantly enhances international health and security.