Biosafety level

• 1. Introduction

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  Over 5,000 accidental laboratory infections and 190 deaths had been recorded worldwide by 1999, according to Health Canada, and the biosafety level system is the long answer to that record. A biosafety level, also called a pathogen or protection level, is a set of containment precautions for isolating dangerous biological agents inside an enclosed laboratory. The scale runs from level 1, the lowest, to level 4, the highest.

  In the United States, the Centers for Disease Control and Prevention lay the levels out in a publication known as Biosafety in Microbiological and Biomedical Laboratories. The European Union defines the same levels in a directive. Canada calls them Containment Levels. Many people also know them as P1 through P4, which is why a level 3 workplace is often called a P3 laboratory.

  Between the bottom rung and the top, the demands climb from everyday habits to extensive training, sealed rooms and strict control over who may enter. Who first built a box to shield a researcher from a dangerous culture? What separates a classroom bench from the most guarded room on a research campus? And what should a laboratory do with a sample that may have come from another world?

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• 2. Secrecy at Camp Detrick

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  In 1943, a soldier named Hubert Kaempf Jr. grew tired of his military police duties at Camp Detrick in Maryland and found a way out. He transferred to the sheet metal department, which worked with the contractor H.K. Ferguson Co. There, under the direction of Arnold G. Wedum, he fashioned the first prototype of a Class III cabinet, the maximum containment type of biosafety cabinet. Wedum led industrial health and safety for the United States Army Biological Warfare Laboratories from 1944 to 1969.

  On the 18th of April 1955, fourteen representatives met at Camp Detrick, in Frederick, Maryland. They came from the three principal biological warfare laboratories of the U.S. Army. Their goal was to trade experience on biosafety, and on the chemical, radiological and industrial hazards that all three sites shared. Because of the work involved, attendance required top level security clearances.

  Beginning in 1957, the conferences added unclassified sessions beside the classified ones, so that safety knowledge could travel further. Even so, no conference took place at a government installation outside a biological warfare program until 1964.

  By 1966, delegates from universities, private laboratories, hospitals and industrial complexes had joined representatives of every federal agency that sponsored or conducted research on disease-causing microorganisms. Participation kept widening through the 1970s. In 1983, people began discussing a formal organization. The American Biological Safety Association was officially established in 1984, and its constitution and bylaws were drafted that same year. By 2008, its professional association counted some 1,600 members.

  Meanwhile, in Australia, a question put to a laboratory chief in 1977 would carry these American ideas in a new direction.

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• 3. Exporting the Standard

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  In 1977, Jim Peacock of the Australian Academy of Science asked Bill Snowdon, then chief of the CSIRO's Australian Animal Health Laboratory, for a favor. Peacock wanted staff at the laboratory, known as AAHL, to review two freshly released sets of bio-containment infrastructure requirements. One came from the United States National Institutes of Health and the other from Britain. The hope was to recommend that Australian authorities adopt one of them.

  AAHL project manager Bill Curnow and engineer Arthur Jenkins carried out the review. They drafted outcomes for each of the levels of security. The Australian Academy of Science adopted their drafts, and those drafts became the basis for Australian legislation. The laboratory itself was notionally classified as "substantially beyond P4". It opened in 1985 at a cost of AU$185 million, built on Corio Oval.

  That laboratory now stands in Geelong, Victoria, and was renamed the Australian Centre for Disease Preparedness in April 2020. It can house animals from large experimental species down to insects. Its zones can be run at different containment levels at the same time. The source calls its design arguably the most researched design and construction project ever, and the antecedent of such facilities developed since the 1980s. Curnow gave technical reviews to Canadian, Indian, UK and French authorities, and he advised Dr Jerry Callis in consultations for the UN Food and Agriculture Organization.

  Canada's own flagship came next. A 2007 scientific review paper stated that the Canadian Science Centre for Human and Animal Health, designed in the early 1990s, "has become the prototype for modern BSL4 laboratories". Its National Microbiology Laboratory in Winnipeg began operating in 1999, run jointly by the Public Health Agency of Canada and the Canadian Food Inspection Agency.

  In 2003, the Chinese Academy of Sciences approved the construction of mainland China's first BSL-4 laboratory, at the Wuhan Institute of Virology. The institute's National Bio-safety Laboratory was built in 2014 for 300 million yuan, about US$44 million, with help from the French government's CIRI lab. The institute itself dates to 1956, and it already hosted BSL-3 laboratories before the new facility arrived.

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• 4. Benches and Bleach

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  The first biosafety level asks workers for a pair of hand washes, one on entering the lab and one on leaving. It suits well-characterized agents that do not cause disease in healthy humans and pose minimal hazard to staff or surroundings. Work can happen on standard open benches with no special containment equipment. Eating and drinking are generally forbidden, and protective gear is required only when someone might be exposed to hazardous material.

  Waste gets its own routine. Potentially infectious material must be decontaminated before disposal, either by adding a chemical such as bleach or isopropanol or by packaging it for decontamination elsewhere. The lab needs a door that can be closed to limit access, but it does not have to be isolated from the rest of the building. Typical organisms include non-pathogenic strains of Escherichia coli and Staphylococcus, Bacillus subtilis and Saccharomyces cerevisiae. Because such labs are easy and safe to maintain, high schools and colleges generally use them for teaching.

  Level 2 keeps every level 1 precaution and adds more. Its defining rule is that "laboratory personnel have specific training in handling pathogenic agents and are directed by competent scientists." Access is limited while work is under way. Procedures that could produce infectious aerosols or splashes move into biological safety cabinets or other physical containment equipment. Contaminated sharp items demand extreme care.

  This level covers agents of moderate hazard, including microbes that cause mild disease or are hard to catch by aerosol in a lab. American Risk Group 2 examples include seasonal influenza, SARS-CoV-2, hepatitis A, B and C viruses, and HIV. The list continues with pathogenic strains of Escherichia coli and Staphylococcus, Salmonella, Plasmodium falciparum and Toxoplasma gondii. The European Union departs from the American list by placing HIV and hepatitis B G in Risk Group 3, which belongs at level 3.

  Prions, the agents behind prion diseases such as vCJD, are typically handled at level 2 or higher. There is no evidence of aerosol transmission, and the infective dose is relatively high. In a facility that cares for vulnerable animals, however, handling animal-infective prions would call for level 3 conditions.

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• 5. Behind Two Doors

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  Tuberculosis, plague, yellow fever and West Nile virus all appear on the roster for biosafety level 3. This level fits microbes that can cause serious and potentially lethal disease through inhalation, and the work may take place in clinical, diagnostic, teaching, research or production facilities. The roster also includes Francisella tularensis, Chlamydia psittaci, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, SARS-CoV-1, MERS-CoV, Coxiella burnetii, Rift Valley fever virus, Rickettsia rickettsii, chikungunya, and several species of Brucella.

  People come first in the extra rules. Each lab must draft its own biosafety manual describing how it will comply with every safety requirement. Staff receive medical surveillance and are offered relevant immunizations where available, which lowers the chance of an accidental or unnoticed infection. All procedures with infectious material happen inside a biosafety cabinet. Workers wear solid-front protective clothing, meaning gowns that tie in the back. Those gowns never leave the lab and are discarded or decontaminated after each use.

  The building matters just as much. Two sets of self-closing doors stand between the lab and the outside, to reduce the chance that aerosols escape. The entrance must be kept apart from parts of the building with unrestricted traffic. Carpets are banned, and seams in floors, walls and ceilings are sealed so that cleaning and decontamination are easy. Windows are sealed as well.

  A ventilation system pushes air from the clean areas toward the areas where infectious agents are handled. Air from the lab must be filtered before it can be recirculated, a requirement that level 4 extends to every kind of waste.

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• 6. Suits and Showers

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  A worker leaving a biosafety level 4 laboratory passes through a chemical shower, then a room for removing the positive pressure suit, and finally a personal shower. This highest level is meant for agents that could easily spread by aerosol inside the lab and cause severe to fatal disease, with no vaccine or treatment available. Labs are generally built in one of two styles, the cabinet laboratory or the protective-suit laboratory.

  In a cabinet laboratory, all work takes place inside a Class III biosafety cabinet. Anything leaving the cabinet is decontaminated by passing through an autoclave or a tank of disinfectant. The cabinets need seamless edges for easy cleaning, and neither the cabinet nor its contents may have sharp edges that could damage the gloves. In a protective-suit laboratory, personnel in positive pressure suits do all their work in a Class II biosafety cabinet.

  Access is tightly restricted to trained and authorized people, and every entry and exit is recorded. As at level 3, the lab is kept apart from areas with unrestricted traffic, and air always flows from clean areas toward the zones where infectious agents are handled. Airlocks guard the entrance. All waste, including filtered air, water and refuse, must be decontaminated before it can leave the facility.

  Marburg virus, Ebola virus, Lassa virus and Crimean-Congo hemorrhagic fever are handled here, all of them known for causing viral hemorrhagic fever. So are Hendra virus, Nipah virus and some flaviviruses. Smallpox virus is also worked on at this level, but only at the Centers for Disease Control and Prevention in Atlanta and at the State Research Center of Virology and Biotechnology in Koltsovo, Russia.

  A poorly characterized pathogen that looks closely related to a dangerous one often lands here too. It stays at this level until researchers gather enough data either to confirm the placement or to allow work at a lower level.

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• 7. Samples From Other Worlds

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  NASA and ESA are working together on the Mars Sample Return campaign, which is due to deliver Martian samples to Earth in the early 2030s. Any sample-return mission from a Category V body must send its cargo to a facility rated BSL-4. The difficulty is that none of the world's current BSL-4 facilities offers the level of cleanliness that such pristine samples require. A dedicated facility is therefore needed to curate restricted, potentially biohazardous extraterrestrial material.

  Designing it means containing the unknown. Nobody can say how large a hypothetical alien microorganism would be. Ideally, the facility would filter particles down to 10 nanometers. Releasing a particle of 50 nanometers or larger is unacceptable under any circumstance.

  The pressure is mounting because a Sample Receiving Facility is expected to take 7 to 10 years from design to completion. Planners recommend a further two years for staff to become proficient and settle into the building.

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• 8. Counting the Labs

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  On the 4th of October 2007, the U.S. Government Accountability Office published a report identifying 1,356 CDC and USDA registered BSL-3 facilities across the United States. About 36% of them sat in academia. The report also found 15 BSL-4 facilities in the country, nine of them at federal labs. A 2015 study by USA Today journalists identified more than 200 lab sites accredited at level 3 or 4.

  No single American agency oversees all of this. Level 3 and 4 labs fall under the CDC, the USDA or another federal agency, depending on the pathogens they handle, so nobody tracks the total. Laboratories that work with declared select agents must be inspected periodically by the CDC or USDA. They must also follow set standards and keep up ongoing education on biosecurity and biosafety policies, as the law requires. Registered high-containment labs must adhere to Department of Defense standards. A North Carolina Mosquito & Vector Control Association study highlighted safety concerns and noted that academic funding accounts for 72% of the money for these labs.

  Globally, 42 BSL-4 facilities were operating as of May 2021, with a further 17 planned or under construction. Local opposition has shaped some of them. The National Institute for Infectious Diseases in Musashimurayama, Tokyo, was built in 1981 yet ran at BSL-3 until 2015 because nearby residents objected. A facility at RIKEN in Tsukuba, completed in 1984, was never operated as BSL-4 for the same reason.

  Politics has also reached the labs. Starting with the 2020 COVID-19 pandemic near the Wuhan Institute of Virology, biocontainment work became politicized, particularly in the US Senate through the efforts of Rand Paul. On the 25th of October 2022, Russia raised questions at the United Nations about biolabs in Ukraine.

  In April 2023, Sudan's descent into civil war alarmed the World Health Organization over its National Public Laboratory. Rival factions fought over the area, and the laboratory's staff were pushed out so a military base could be installed on its premises. The facility held only organisms rated at BSL-2 at the time.

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