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USDA Official Points to Science as Key Design Factor

Bio-Safety Levels Help Reduce the Risk of Laboratory Infection

Published October 2002

"During the last few decades there have been dramatic advancements made in the technology used to contain microbes in laboratory settings," says Michael Kiley, Ph.D., Research Program Safety Officer with the Agriculture Research Services of the United States Department of Agriculture in Beltsville, Md.

He points out that anyone involved in lab design or facility management should embrace new technologies, but should also remember that the ultimate reason behind the technology goes back to the nature of the microbes being studied. In laboratories there is a clear link between the engineering of technology and the agents involved.

"Good lab design can definitely help to facilitate the containment process, but it can never take the place of scientists trained in the proper procedural steps to contain microbes," adds Dr. Kiley, who learned this firsthand when he began his career in 1978 at the Centers for Disease Control studying the hemorrhagic fever viruses.

Such deadly viruses continue to make headlines, including newly discovered strains of the West Nile virus in the U.S. and abroad. In addition, recent attacks using laboratory-produced Anthrax as a weapon have heightened concerns of both bio-safety and bio-security. Several recently passed laws address these concerns, including the USA Patriot Act of 2001, which has provisions on how laboratories can work with "select agents and toxins," and the Bio-terrorism Preparedness Act of 2001, which is designed to control the use and distribution of so called "select agents," defined as biological agents thought to pose a bio-terrorism threat to the United States.

"It is crucial that we continue to find scientists willing to work with these organisms and that the work continue in a safe and effective manner," says Dr. Kiley, who explains that these organisms can often have devastating effects on agriculture, as well as animals and humans. As a key example he points to the trickle down effect felt by Midwest corn farmers who lost $1.5 billion in sales to Taiwan when the Taiwanese pork industry was crippled by foot and mouth disease several years ago.

Bio-Safety Levels

With more than 24 million people working in some phase of agriculture within the U.S., it is one of the largest employers within the country. Sales and exporting of food and fiber products account for more than 13 percent of the U.S. gross national product and each year alone, livestock exports typically total from $6 to $10 billion.

To help protect these valuable resources the U.S. Public Health Service established a series of bio-safety levels (BSL) designed to help reduce the risk of laboratory infection or the release of microbes to the environment. The levels define a set of parameters for work practices, containment devices, and construction technology for use with specific microbes. There are levels 1 through 4, with higher levels pertaining to more pathogenic microbes, which require stricter containment procedures. (See box, Bio-Safety Levels)

Another level, known as "BSL-3 Agriculture," has added requirements to protect American agriculture, both animals and crops, from exposure to pathogens and potential infection. This is the strictest level pertaining to agriculture. Some of the criteria taken into consideration to categorize agents into a particular level include the agent's pathogenicity or ability to cause disease, its biological stability, the concentration of the organism, and whether or not there is an effective vaccine or therapy available.

"Most high-containment labs usually deal with viruses," says Dr. Kiley who calls viruses the ultimate parasites because they have no energy source of their own and are absolutely dependent on the cellular mechanisms to replicate.  "In fact, many of the current lab safety and design practices are actually based on the nature of viruses," he notes.

Agent Types

Viruses contain only one type of nucleic acid (either DNA or RNA, but not both) and then a protein shell coating to protect the viral genetic information. A virus has no energy source. Instead, the virus particle inserts its nucleic acid or genetic information into the cell and uses the cell processes to make viral proteins that are responsible for manufacturing new particles.

"The contact of an agent with a host is not necessarily enough to cause a viral infection," says Dr. Kiley. "Typically you need parameters such as the right number of organisms, the right hosts, the right portal of entry, and the right tissues to come in contact with the correct agents and these parameters are different for each agent."

The West Nile virus is an example of a unique transmission characteristic. West Nile requires a reservoir, in this case birds, which are the amplifying hosts. People and animals can become infected incidentally by the bite of a mosquito, but apparently do not make enough viruses to cause transmission to other animals. Horses, for example, can't pass along the agent because they don't build up sufficient amounts in the blood for the mosquito to transmit to the next host.

"Researchers and scientists who deal with agents such as viruses have helped to eradicate numerous animal diseases within the U.S. such as foot and mouth disease and cattle tick fever," says Dr. Kiley. "They have also been instrumental in learning more about emerging animal diseases such as Lyme disease, E. coli, and the West Nile virus."

Safety Procedures and Design

Accident prevention is a concern for every lab, but it should be top priority for high-containment labs that deal with agents classified at bio-safety levels 3 and 4 since workers are at greater risk from accidents such as needle sticks, injury by sharp blade or glass, spills, sprays, and even animal bites and scratches.

At these levels, following proper procedural safeguards and implementing safe work practices are the foundation for lab safety. Key examples include restricting access to lab and work areas, conducting experiments in class 3 cabinets or isolation suits with their own air supply, and following the proper procedures for waste disposal and decontamination.

"While good design can help to reduce accidents, especially those associated with environmental factors, design is not a substitute for good laboratory practices," says Dr. Kiley, who points to the staff at CDC's Building 9 (the first bio-safety level 4 laboratory that required isolation suits) as a prime example of safe work standards. The staff worked for more than 10 years with no safety or cross contamination problems even though they were using multiple agents and multiple animals.

By Amy Cammell

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Biography

Michael Kiley, Ph.D., is the Research Program Safety Officer with the Agriculture Research Services of the United States Department of Agriculture (USDA) in Beltsville, Md. He received his Ph.D. in microbiology and virology from the University of Virginia in 1972 and has held positions at the University of Michigan, University of Nevada, the Centers for Disease Control, the Salk Institute, the National Institutes of Health, and Johns Hopkins University. He has also been a visiting scientist at Pirbright in England and the National Institutes for Virology in South Africa. Dr. Kiley has served as a consultant for the design of new facilities and as a senior scientific advisor for the Federal Laboratories Project in Winnipeg, Canada. He is currently involved in the planning of a major new USDA research facility involving large amounts of BSL-3 and BSL-3 Ag space.

This article is based upon a presentation Dr. Kiley gave at Tradeline's International Conference on Bio-Containment Facilities in April 2002.




For more information

Michael P. Kiley, Ph.D.
ARS Research Programs Safety Officer
United States Department of Agriculture
5601 Sunnyside Ave., Rm. 4-2174
Beltsville, MD 20705-5138
Ph. 301-504-4734
MDK@ars.usda.gov




Resources

Bio-Safety Levels:

BSL-1: pertains to agents of minimal hazard. There is no need for containment devices and the lab areas are not separated from other work areas. Examples: B. subtilis, Naegleria gruberi

BSL-2: pertains to agents of moderate hazard. Certain procedures within the lab must be done in bio-safety cabinets and access is limited when working with agents. Examples: Hepatitis B, Salmonellae.

BSL-3: pertains to agents that can have serious or lethal consequences. Access is severely limited and all work is done in bio-safety cabinets since these agents have a high mortality rate.  Labs working with these agents must have a separate anteroom, specific waste disposal/ decontamination systems, directional airflow, and surfaces capable of decontamination. Examples include M. tuberculosis, Yellow Fever, and many zoonotic diseases, which infect both man and animals, such as Tuberculosis, Rabies, West Nile virus, and Anthrax. However, with the bio-terrorism aspects, Anthrax becomes a level 4.

BSL-4: pertains to agents that pose a high risk of life threatening disease.  All work within labs working with these agents is done in class 3 bio-safety cabinets by scientists or researchers wearing isolation suits. The lab facility is separated from other work areas and access is strictly controlled. Examples include Lassa fever and Ebola.

BSL-3 Agriculture: pertains to agents that pose a high risk of infection and have the potential for internal transmission. These include a wide variety of animal disease threats both domestic (endemic) and foreign (exotic) and all of the emerging zoonotic diseases.

In addition to the containment requirements in the previous levels discussed, BSL-3 Ag has specific agricultural enhancements including: decontamination/sterilization of liquid effluent, HEPA filter treatment of exhaust and/or supply air, provision for personnel "shower out" capability, and some restriction on contact with domestic animals.




Isolation Suit

High-containment labs that deal with agents classified as bio-safety levels 3 and 4 often require workers to conduct experiments wearing isolation suits equipped with their own air supply. If isolation suits are not available, bio-safety containment cabinets can also be used. (Photo courtesy of the United States Department of Agriculture.)

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