BSL-3 FAQ

The National Institutes of Health (NIH) defines four Risk Groups that are classifications to describe the relative hazard posed by infectious agents or toxins in the laboratory:

• Risk Group 1 (RG1) - Agents that are not associated with disease in healthy adult humans. This group includes a list of animal viral etiologic agents in common use. These agents represent no or little risk to an individual and no or little risk to the community.
• Risk Group 2 (RG2) - Agents that are associated with human disease which is rarely serious and for which preventive or therapeutic interventions are often available. These agents pose a moderate risk to an individual but a low risk to the community.
• Risk Group 3 (RG3) - Agents that are associated with serious or lethal human disease but typically have some sort of treatments available. These agents represent a high risk to an individual but a low risk to the community.
• Risk Group 4 (RG4) - Agents that are likely to cause serious or lethal human disease for which preventive or therapeutic interventions are not usually available. These agents represent a high risk to the individual and a high risk to the community.
• Select Agents and Toxins: A list of biological agents and toxins that have been determined by the Department of Health and Human Services (HHS) to have the potential to pose a severe threat to public health and safety, to animal and plant health, or to animal or plant products. There are currently 68 select agents and toxins regulated by the Federal Select Agent program.

The Centers for Disease Control and Prevention (CDC) defines four Laboratory Biosafety Levels that guide the standard microbiological practices, safety equipment, and laboratory facilities required for activities involving infectious microorganisms, toxins, and laboratory animals.

Biosafety Level 2 (BSL-2) labs are suitable for work with RG2 agents, including: most strains of influenza, Staphlococcus aureus, Salmonella sp., pathogenic strains of E. coli, Klebsiella sp., adenovirus, rhinovirus, dengue fever virus, Zika virus, measles virus, Listeria sp, and many attenuated strains of higher risk pathogens such as Mycobacterium tuberculosis (Mtb), Yellow fever virus, and HIV (specifically lentivirus, which is currently used on campus by dozens of researchers for molecular biology experiments).

Biosafety Level 3 (BSL-3) labs are suitable for work with RG3 agents that may cause serious or potentially lethal disease through inhalation, including: Bacillus anthracis, Yersinia pestis, Brucella sp., Mycobacterium tuberculosis, and SARS-CoV-2. Preventative or therapeutic interventions may be available for infectious agents studied in BSL-3 laboratories. Animal Biosafety Level 3 (ABSL-3) refers to laboratory practices suitable for work with animals infected with such agents.

BSL-3 laboratories operate safely alongside other research facilities on university campuses across the country, including many of our peer institutions such as Duke, Emory, Harvard, NYU, Stanford, Tulane, UC-Berkeley, UCSF, USC, and Washington University-St. Louis. Two academic research institutions, Boston University and University of Texas Medical Branch-Galveston, support and operate BSL-4 laboratories on their main campuses, which are suited for working with RG4 or Select Agents.

The University of Chicago also has more than 200 BSL-2 labs on its campus in Hyde Park using dozens of human pathogens and additional pathogens that are infectious to plants and animals.

An element of risk is associated with all laboratory-based research. Multiple hazards on campus can be misused – biological, chemical, or radiological – no matter the biosafety level, however, such research can be conducted safely and responsibly, as demonstrated by our many peer institutions mentioned above. In many ways, BSL-3 research is safer than BSL-2 work, due to the much more rigorous oversight, training and safety protocols described below.

UChicago operates BSL-3 space on the seventh floor of the Cummings Life Sciences Center (CLSC) in Hyde Park. This space previously housed BSL-3 research on campus until these activities moved to the Howard Taylor Ricketts Laboratory (HTRL) at Argonne National Laboratory when it opened in 2009.

There are plans to commission additional new BSL-3 space on the sixth floor of the CLSC. Details for that facility will be shared in the same manner as those plans develop.

Construction on the new laboratory space began in early 2023, and the lab went live on March 4, 2024.

Initially, Mycobacterium tuberculosis (Mtb), the organism that causes tuberculosis, both in vitro and in rodent models. The Department of Microbiology intends to recruit more faculty who will study additional BSL-3-level pathogens, including viruses. Building occupants will be informed when additional organisms will be added to the approved protocols of the CLSC facility. 

While Mtb is classified as a BSL-3-level pathogen, as many as 2 billion people worldwide live with latent tuberculosis infection. There is a very low conversion rate from infection to clinical tuberculosis disease, and treatment is readily available.

The Howard Taylor Ricketts Laboratory (HTRL) was built with support from the National Institute of Allergy and Infectious Diseases (NIAID) and is one of twelve Regional Biocontainment Laboratories with state-of-the-art BSL-3 facilities. The facility is well-suited to support research involving Mycobacterium tuberculosis, and space has been allocated to support such research. The remaining space is used to respond to emerging infectious pathogens such as SARS-CoV2 (as required by NIAID), and to perform Select Agent research that cannot be conducted elsewhere at the University of Chicago.

The Biological Sciences Division and the University of Chicago are broadly committed to building a nationally renowned program to study and treat emergent infectious diseases, and the availability of BSL-3 and ABSL-3 facilities on campus is a competitive advantage in this recruitment effort.

The Marjorie B. Kovler Viral Oncology Laboratory in Hyde Park formerly supported a research program managed at BSL-3 protocols, although the facility does not meet current BSL-3 standards. This lab space is currently fully occupied by BSD core facilities and faculty from the Pritzker School of Molecular Engineering.

In 2009, a University of Chicago researcher died from a laboratory-acquired infection with an attenuated strain of Yersinia pestis (KIM D27). The strain had not been known to have caused laboratory-acquired infections or human fatalities, and the work was being conducted in a BSL-2 facility. Following investigation by the University and public health authorities, the researcher was later found to have a genetic condition that made him uniquely susceptible to infection, making the attenuated stain fatally virulent. You can find more information about this case from the CDC.

In 2011, a researcher working in another BSL-2 facility acquired a skin infection with Staphylococcus aureus, requiring hospitalization. Later investigation found that the infection was likely acquired from a surface that had not been properly decontaminated.

Following the two lab-acquired infections, the University of Chicago established a campus wide Office of Research Safety (ORS) that partners with researchers across campus to ensure that laboratory research is conducted safely and according to federal and institutional guidelines. The biological safety team provides training and guidance to investigators, staff, and students performing laboratory research with hazardous biological materials. Their team of experts oversees all University-sponsored research involving microorganisms that pose hazards to humans.

ORS staff work closely with the Biological Sciences Division and research groups working in the BSL-3 spaces to ensure that all ongoing research is conducted in a way that minimizes risk to both laboratory personnel and the surrounding environment. This includes reporting and mitigation efforts in the event of laboratory incidents and coordinating with BSD Facilities Services on BSL-3 security access (see #11 for more about additional security measures in the building).

Building upon years of experience monitoring the Ricketts BSL-3 facility, the ORS works closely with the Institutional Biosafety Committee (IBC) that consists of subject matter experts (UChicago faculty, veterinarians, clinicians) as well as community members who have no affiliation to the University. This group assesses risk on a regular basis, and IBC protocol review and approval is required for all research involving pathogenic microorganisms, whether human, animal or plant pathogen.

The ORS integrates its annual laboratory inspection program with the IBC protocol review and approval process. In this context, the laboratory inspection program includes the following elements:

• Discussion with lab members to determine what infectious or recombinant agents are being used in the lab
• Review of the lab’s IBC protocol(s)
• Walkthrough of the lab space with at least one member of the lab familiar with the research
• Assessing training requirements and ensuring everyone in the lab is current in their training
• Successful completion of the inspection requires addressing any concerns by ORS. If this isn’t done in a timely matter, the lab is reported to the Dean

In general, ORS and the BSD encourage a strong culture of safety and accountability for all lab spaces throughout campus, regardless of their biosafety level.

• Laboratory staff should always follow safety protocols (not just during inspections) and encourage accountability among their colleagues.
• Staff should be respectful of other building occupants. While they may not work in a BSL-3 lab themselves, research staff should avoid giving the impression of lax safety standards by wearing PPE into common areas, for example, or allowing unknown individuals to “piggyback” access through secured doors, elevators, and stairwells.

Once the Office of Research Safety has responded to a reported incident and assessed the situation, BSD administration will send email communications with pertinent details to those working in the building, including, but not limited to:

• The timing and nature of the incident
• Impact on neighboring labs
• Remediation activities
• Findings of investigations into the incident
• Changes to protocols, systems, or facilities necessitated by the incident, if needed

The Cummings Life Sciences Center is an active research and classroom facility. Due to the diverse group of faculty, students, research personnel, and administrative staff that need to access to the building, it cannot be secured simply at the ground floor entrances alone.

The ORS and the BSD Facilities design team has implemented five tiers of security for the building and the lab facilities on its upper floors:

1. Restricted proximity card access for BSD staff at the north and south doors. Students who need to attend classes in Cummings will also be granted access in coordination with the registrar’s office.
2. Restricted proximity card access for BSD staff to the elevators.
3. Restricted proximity card access to the 7th floors from all elevators and stairwells, limited to only those staff who need access to labs located on that floor.
4. Restricted keypad access to BSL3 suites.
5. CCTV camera monitors in the building lobby and hallways on the 7th floor.

Commissioning BSL-3 space involves specific changes to control access and movement through the labs, processes for cleaning, autoclaving, and decontamination, installation of enclosed, ventilated biosafety cabinets for working with pathogens, and changes to ventilation to separate air flow from the rest of the building. This also includes contingency plans to monitor building systems for power loss or other malfunctions, and mechanisms for isolating the lab space in the event of a biosafety incident, fire, or natural disaster.

In addition to facility enhancements required for BSL-3 laboratories in Appendix A below and security measures detailed in #11 above, management of BSL-3 labs differs from the management of BSL-2 labs in the following ways:

1. At least two lab inspections a year compared to annually for other labs
2. ORS will require and approve all inactivation protocols before use
3. Removal of materials from the lab will be tracked
4. Transport of materials within Hyde Park will be tracked
5. Waste will be autoclaved prior to disposal and incineration by the University’s biomedical waste contractor

Source: UChicago Office of Research Safety