Outbreak Breakthrough

Advanced disease research is conducted every day at the UTHSC Regional Biocontainment Lab.

Fu Zen, an animal husbandry technician, cleans animal cages inside a biosafety cabinet.

photograph courtesy UTHSC

With outbreaks of Swine Flu and West Nile Virus almost annually, and fictional worldwide epidemics spreading fear through box office blockbusters, it might seem like microbial organisms are starting to outsmart humans. But science is fighting back, and one of the key locations for the effort is in Memphis.

The University of Tennessee Health Science Center (UTHSC) Regional Biocontainment Lab, operational since late 2009, is central to advanced development of new drugs, vaccines, and diagnostics to protect the general population from infectious diseases and bioterrorism. It was the first of several buildings in the development known as UT-Baptist Research Park, a biotech hub located in the heart of the Memphis Medical Center designed for the highly specialized needs of Memphis’ bioscience community (for more information on UT-Baptist Research Park, go to mbqmemphis.com).

Memphis was chosen as a location for one of 13 Regional Biocontainment Laboratories (RBLs) in the United States by a committee in early 2002 in part because of the city’s history of advancement in research and development of vaccinations for infectious diseases in the 1960s, including strep and staph, under the tutelage of Dr. Gene Stollerman and Dr. Edwin Beachey. Along with its rich history in vaccination development, Memphis provided the ideal combination of experienced genetics groups, researchers, and key regional resources such as FedEx, the courier for the vast majority of biomedical lab shipments.

From inception, the UTHSC RBL has been funded and approved by the National Institute of Allergy and Infectious Disease (NIAID), is designed to resist earthquake loads, and it meets the standard operating procedures for the Centers for Disease Control and Prevention (CDC), the U.S. Department of Agriculture, the National Institutes of Health (NIH), and the Department of Defense. In fact, the RBL’s cooperation and compliance with protocol has earned the Memphis facility a three-year renewal rate from CDC “check ups” — the highest and most rare renewal rate for RBLs. “The CDC loves us like crazy because we’re a tight, well-run facility,” says Dr. Gerald I. Byrne, Ph.D. and director of the UTHSC RBL.

The UTHSC RBL focuses mainly on respiratory infectious diseases, which makes air handling a key factor. At every stage of development and construction, the RBL building was inspected and approved by the NIAID, the CDC, and a third-party investigator before becoming licensed and operational.

While much is different from its cinematic bio-lab counterparts as seen in Contagion or Outbreak, there are a few similarities, including the importance of air handling and personal protective equipment (PPE). The UTHSC RBL is a Biosafety Level 3 (BSL-3) containment — on a scale of 1 to 4 where 4 is the most dangerous. It does not ever deal with BSL-4 materials.

“BSL-2s can be upgraded to become 3s, but 3s can never be retrofitted to become 4s [because of the way they’re designed],” says Jennifer Stabenow, facility manager of the UTHSC RBL.

Most labs seen in disaster movies would be considered BSL-4 containment, and they would include watertight labs. Byrne says, “[In a BSL-4 lab] the researcher is in an air-tight suit in which air is pumped directly into the suit [not filtered through a respiratory mask, like a BSL-3]. If you left a faucet running in [a BSL-4], the water would just rise to the ceiling and never leak.”

Instead, the UTHSC RBL focuses mainly on respiratory infectious diseases, which makes air handling a key factor. At every stage of development and construction, the RBL building was inspected and approved by the NIAID, the CDC, and a third-party investigator before becoming licensed and operational. There are at least three levels of restricted containment, air is filtered extensively coming in and out of the laboratory, and the temperature and pressure of the air are adjusted at each stage. Additionally, PPE jumpsuits, gloves, and masks are required when entering the containment areas.

This means that several restricted-access corridors — followed by three separate, restricted-access chambers in which the air is filtered every hour, temperature is adjusted, pressure decreased, and PPE gear is issued — separate the outside world from absolutely anything remotely contaminated or infected.

Furthermore, researchers are not just working in a securely contained room but also a biosafety cabinet, or enclosed workspace, that also has ventilated air flow. Even the cages of the healthy, uninfected animals, which are already enclosed in a separate area several corridors away from the infected animals, are equipped with special air-tight filters that pump clean air in and out. “We have a tremendous amount of redundancy,” says Byrne. “An appropriate analogy would be the space station: It’s built for function, not comfort.” It’s all just part of the CDC regulations.

The protocols seem to work: Even with 14,000 individuals coming in and out of BSL-3 labs across the country every day, there is virtually zero risk of contamination to researchers or neighboring communities.
Though it may seem like the researchers in the RBL spend all of their time just scrubbing in and out of the “containment” area due to the strict protocol of the CDC’s standard operating procedures, numerous advanced research projects use the RBL area for its state-of-the-art equipment and resources. Currently, investigators are working on projects involving multidrug resistant tuberculosis, tularemia (specifically francisella tularensis), burkholderia pseudomallei, SARS, and Chlamydia infections, and the RBL is in the process of recruiting more researchers and students for various samples it will acquire soon.

Byrne says since it is a publicly funded, publicly run facility used to protect the general population, the UTHSC RBL is essentially an open book. The ultimate goal of the majority of its research is to be published; so, minus the details of building security and location and amount of inventory, Byrne and Stabenow are happy to talk about their work. They even give tours to show the Mid-South community that “the reality of these labs is so much different and more routine than the movies.”

In fact, while the UTHSC RBL houses both BSL-2 and BSL-3 laboratories, its animal lab (ABSL-3) takes up the largest share of square footage.

The work might be routine, but it’s not accessible to just anyone. A mere 12 people make up the permanent staff at the UTHSC RBL, but it can have as many as 80 people conducting research in its laboratories on any given day. Investigators mainly consist of UTHSC professors and students in the College of Medicine and College of Pharmacy, but it also rents allotted spaces to independent contractors and private sectors for a fee.

Whatever the reason for the visit, everyone who walks through the door goes through a degree of training. The facility mandates initial training, annual refreshers, and practical training depending on the nature of research.

The research and development of new drugs and vaccines is critical to every RBL, but the UTHSC RBL is unique from other labs in its experience in isolating specific genes in mice to better understand the link between genetics and susceptibility to infections. Genetic research and experience is key in the prevention of infectious diseases because why certain people are more prone to specific infections and why certain people experience more severe reactions is directly linked to their genes. If the researchers at the UTHSC RBL can identify certain genes as higher-risk, then they know who is more susceptible to infection, who to cure first, and how to better develop a cure.

Another crucial component to the UTHSC RBL is that while most people are only highly aware of human pathogens that cause infections, these researchers have a broader mindset. “It’s not just the human impact, it’s the impact on agriculture and economy,” Stabenow says. “Anything that could decimate our herds or livestock would be a huge issue.”

In fact, while the UTHSC RBL houses both BSL-2 and BSL-3 laboratories, its animal lab (ABSL-3) takes up the largest share of square footage. Byrne explains that pathogens that infect agriculture and livestock are also key to bioterrorism because of specific strains called “species jumpers.” For example, swine are a “mixing bowl” which can produce “species jumpers,” and these pathogens are almost always the cause of pandemics. That is why the research conducted at the UTHSC RBL is so important even though it isn’t the kind of BSL-4 lab that tests monkeys.

Byrne and Stabenow’s focus and drive are rapidly making the UTHSC RBL one of the finest labs in the country. “The people we have here believe it’s not a job but a mission, and that attitude has carried us along in our success,” Byrne says. “We have an NIH-mandated public health service here, and we take that very seriously. The goal is to develop deliverables for important infectious diseases on a local, national, and worldwide level.”

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