Frequently Asked Questions About Biodefense

Q: What are the various biosafety levels and what does each one imply?

Biosafety levels provide guidelines for practices, safety equipment, and facility layout to ensure safe handling of materials in biological laboratories.(1)

There are four biosafety levels (BSL), which have increasingly stringent security and containment practices. The safety levels are determined based on the agents used in research and the ways they affect the human population. Level 1 facilities have the fewest requirements for safety equipment, while Level 4 facilities have the most.

In brief, the agents used, safety equipment, and secondary barriers in the facilities for each level breakdown as follows. Level 1 is not known to cause health problems in human adults (with the possible exception of the elderly and adults with immune system deficiencies). No safety equipment is required, though facilities must have sinks for hand washing.

Level 2 facilities research agents that are associated with human disease; hazards are restricted to ingestion and mucous membrane exposure. Safety equipment for BSL2 facilities are minimal physical containment devices, lab coats, gloves, and goggles. Sinks and an autoclave are also required.

BSL3 facilities work with indigenous or exotic agents that may be transmitted via aerosol; these diseases may be lethal or cause serious health problems. Again, physical containment devices are used, in addition to laboratory clothing, gloves, and respiratory protection (as needed). BSL3 facilities require sinks, an autoclave, physical separation from hallways that lead to exits, double-doors that are self-closing, exhausted air that is not recirculated, and negative airflow into the laboratory.

BSL4 facilities research dangerous and/or exotic agents that have a high-risk of life-threatening disease, hazard aerosol-transmitted infection in the lab, or agents that have an unknown risk of transmission. Safety measures require either a full-body, air supplied suit and a containment securing, airtight apparatus, or use of an airtight container whose only access is via rubber gloves sealed to openings in the container. BSL4 facilities require all of the secondary barriers (i.e. sinks, autoclave, etc.) as mentioned for the other BSL’s, as well as a location in a separate or isolated building; supply and exhaust vacuum and decontamination system; and structural and procedural precautions, such as break-proof windows and emergency plan.

Q: What kinds of organisms are included under Biosafety Levels 3 and 4?

Biosafety Level 3 includes a wide spectrum of viruses, bacteria, and fungal agents. Bacterial agents include: tularaemia, pulmonary and nonpulmonary tuberculosis, glanders, melioidosis, typhoid fever, paratyphoid fever, plague (bubonic, pneumonic, and septicaemic), Q fever, typhus (scrub and epidemic), and Rocky Mountain Spotted Fever. Viral agents include over 170 arboroviruses such as West Nile, yellow fever, and various forms of encephalitis (i.e. Dengue fever and Hantavirus), lymphocytic choriomeningitis (LCM) (neurotrophic strains), Hepatitis B and C, HIV, and Rift Valley fever. Fungal agents in BSL3 include: Coccidioides immitis (which causes pulmonary disease), pulmonary histoplasmosis, and North American Blastomycosis.

Biosafety Level 4 covers a smaller group of pathogens that pose a “high risk of exposure and infection to personnel, the community, and the environment.” These include a number of arenaviruses, filoviruses, and arboroviruses such as: Junin, Marburg, Russian Spring-Summer, Congo-Crimean, hemorrhagic fever, Omsk hemorrhagic fever, Lassa, Machupo, Ebola, Sabia, and Encephalmomyeltis.

The Biosafety Level of each agent is determined by taking several characteristics into consideration. Generally, the BSL3 agents are “indigenous or exotic agents with potential for aerosol transmission, diseases may have serious or lethal consequences.”(2) BSL4 agents are defined as “dangerous/exotic agents which pose high risk of life-threatening disease, aerosol-transmitted lab infections, or related agents with unknown risk of transmission.”(3) Some agents, such as anthrax, are classified at different biosafety levels, depending on the quantity of the agent and the form the agent takes (aerosol, non-migratory, etc).

Q: How many Biosafety Level 4 labs exist in the country and where are they located?

There are currently four Biosafety Level 4 laboratories in the United States. These are: the Centers for Disease Control and Prevention (CDC) in Atlanta; the United States Army Research Institute on Infectious Diseases (USAMRIID) in Frederick, Maryland; the Southwest Institute for Biomedical Research in San Antonio; and the University of Georgia in Athens, which houses a smaller, “shoebox” facility.

The Bush Administration recently announced the construction of at least three new Biosafety Level 4 laboratories—at Boston University Medical Center; the University of Texas Medical Branch in Galveston; and the Rocky Mountain Laboratories in Hamilton, Montana—as well as the expansion of Biosafety Level 4 capacity at the CDC and USAMRIID. USAMRIID is the only Level 4 laboratory currently under military protection.

Q: What goes on in these laboratories and why are they controversial?

Biological defense laboratories study organisms categorized by the federal government as potential agents of bio-terrorism. Much of the work in these facilities falls into one of the following six categories: (1) research on the basic biology and mechanisms of disease causation in select pathogens; (2) identification and intervention into human immune responses to toxicity and infection; (3) creation of systems to rapidly detect the presence of select agents in the environment; (4) development of methods for more effectively diagnosing human exposure to and infection from bio-terrorism agents; (5) creation of new therapeutic interventions for specific as well as broad categories of pathogens; and (6) production of vaccines against specific agents.

Controversies in biodefense research stem from both the secrecy with which it is associated and the difficulty in distinguishing between its offensive and defensive applications. Federally-funded research on biological weapons is marred by a history of secrecy and misinformation, most strikingly in the hidden offensive bio-warfare program carried out by the U.S. military from the beginning of the Cold War through the early 1970s. Over much of the last thirty years, the Department of Defense has provided an annual report to Congress explaining the nature and extent of its biological research program. After this disclosure policy was discontinued in the early 1990s, there has been growing concern about the potential for offensive research in U.S. laboratories.

Q: Is there a list of major accidents in biodefense labs?

Currently, there is no public record of recent breaches of security, infections of lab personnel, transportation accidents, and environmental releases of organisms at bio-containment facilities. However, the Council for Responsible Genetics has documented the following cases:

• In December 2002, a three-hour total power failure undermined the containment systems at an infectious disease laboratory at Plum Island, New York. Workers had to resort to sealing the doors with duct tape, as the air compressors failed.(5)

• Government scientists in 2002 revealed that over two dozen dangerous biological agents including anthrax and Ebola went unaccounted for in the early 1990s at the US Army Medical Research Unit (USAMRIID) in Ft. Detrick, Maryland. The location of these agents, which were subject to removal without authorization, remains a mystery.(5)

• On March 20th, 2003, a package containing the West Nile virus exploded in a Federal Express building in Columbus, Ohio, exposing workers to the possible infection and causing offices to be evacuated.(6)

• FBI investigations and a recent genetic analysis published in Science suggest that dry anthrax spores originally derived from USAMRIID were used in the September 2001 mail attacks that resulted in five deaths and several billion dollars in damage to the US economy.(7)

• In April 2002, a researcher at USAMRIID tested positive for exposure to anthrax spores, which were also released in small quantities into an adjacent hallway and office.(8)

• In March 2000, a microbiologist working with infectious diseases in a Biosafety Level 3 facility at USAMRIID contracted glanders due to accidental exposure. Between 1987 and 1990, two other workers acquired infectious diseases at the same facility.(9)

• In 1998, a research assistant at the Yerkes Primate Center in Atlanta, part of the National Institute of Health's Primate Research Program, died six weeks after being exposed to simian herpesvirus in the
laboratory.(10)

• In June 2003, the U.S. Army unearthed 113 bacteria-containing vials, including live strains of brucellosis and non-virulent anthrax, during an excavation of its Fort Detrick site to eliminate toxic chemicals and hazardous waste.(11)

Q: Where is the new money for this research going to?

Since 2000, annual federal spending on biological defense research has increased more than sixfold. The most significant trend in spending has been the growing biodefense resources devoted to the National Institutes of Health relative to the Department of Defense. In 2003, the Bush Administration is projected to spend $6.5 billion in bio-terrorism preparedness. Of this, $2.9 billion has been specifically designated for biological research and development (R & D). The proposed 2004 budgets of both Congress and the President provide approximately $6 billion in biodefense spending: $3.5 billion for the Department of Health and Human Services ($1.6 billion for NIH biodefense R&D, $1.1 billion for CDC bioterrorism preparedness, and $0.8 for other agencies), $1.3 billion to the Department of Homeland Security ($0.4 billion for a national vaccine stockpile and $0.9 billion for the purchase of countermeasures), and $1.1 billion to the Department of Defense.

In a period of tight government resources, increases in biological terrorism spending inevitably trade off with other public health priorities. Recent emergency preparedness mandates may force several states to divert millions of dollars from social welfare and public service programs. Meanwhile, at the federal level, the $6 billion per year spending estimate has broadly re-directed the energies of key health research agencies away from chronic infectious diseases and toward speculative risks to national security.

Q: Is there an international treaty on biodefense?

The Biological Weapons Convention (BWC), a treaty ratified by 144 nations including the United States and Russia that came into force in 1972, prohibits the production, stockpiling, development, and use of biological weapons. Article 1 of the Convention permits research on dangerous biological agents and toxins that is “peaceful, prophylactic, or protective” in nature. However, distinctions between offensive and defensive applications of research on bioterrorism agents are difficult to establish at numerous stages of the research process. To resolve this dual-use dilemma, in September of 1998, BWC member states began a process of drafting a verification and enforcement protocol to ensure routine declarations of research on biological warfare agents and inspections of declared facilities. Unfortunately, during negotiations in November 2001, the U.S. announced that it would not permit a binding verification agreement to move forward. As a result, international monitoring of biological defense and warfare is unlikely to emerge in the near future.

November 2003

FOOTNOTES

1 Information compiled from “Biosafety in Microbiological and Biomedical Laboratories,” 4th Edition, CDC-NIH, 1999

2 CDC-NIH Biosafety in Microbiological and Biomedical Laboratories, p. 52

3 ibid.

4 Marc Santora, “Power Fails for Three Hours at Plum Island Infectious Disease Lab,” New York Times, December 20, 2002, p. B1

5 Rick Weiss and Joby Warrick, “Army Lost Track of Anthrax Bacteria,” Washington Post, January 21, 2002, p. A1

6 Anonymous, “Package carrying West Nile explodes at Columbus airport,” Associated Press, March 20, 2003

7 Timoty D. Read, et al, “Comparative Genomic Sequencing for Discovery of Novel Polymorphisms in Bacillus anthracis,” Science, June 14, 2002, Vol. 296, p. 2028-2033

8 David Dishneau, “Fort Detrick worker tests positive for anthrax exposure,” Associated Press, April 19, 2002

9 Steve Vogel, “Army Studies Safety at Fort Detrick Lab; Scientists Contracted Potentially Fatal Disease at Biological Defense Center,” Washington Post, May 16, 2000, p. B3

10 "Fatal Cercopithecine herpesvirus 1 (B Virus) infection following a mucocutaneous exposure and interim recommendations for worker protection," Morbidity and Mortality Weekly Report, 47:1073-6,1083, 1998.

11 Lois Ember, “Fort Detrick Cleans Up,” Chemical & Engineering News, June 2, 2003, p. 12