Where the Bad Things Are
A New Home For Pathogens, and the Scientists Who Struggle to Defeat Them

By Mike Martin

In a world plagued by the threat of pandemic influenza, flesh-eating bacteria, multi-drug resistant infections, and potential terror attacks using exotic contagions, the construction of a “biocontainment laboratory” at MU is bound to conjure notions of moon-suited scientists wearing eerie facemasks with military escorts hovering nearby.

It’s the sort of image author Michael Crichton made famous forty years ago this year, with his hit novel-turned-movie, The Andromeda Strain, about a deadly virus from outer space that stumps a group of scientists after wiping out a desert town.

Rest assured, say researchers at MU’s facility, there is nothing to fear — except perhaps the costs of not investigating the potentially deadly pathogens safely contained with the $18-million Regional Biocontainment Laboratory.

Battling the Bugs 

The lab was funded in part by the National Institutes of Health. When the agency held a nationwide competition in 2007 to expand what faciilty director and chief scientist George Stewart terms “America’s biocontainment infrastructure,” they found at MU a hotbed of comparative medical activity. Not only could MU offer a veterinary school, a medical school, and a college of agriculture in close proximity to one another, but also related facilities such as the University’s Veterinary Diagnostics Lab and the National Swine Research Center, RBL’s next-door neighbor.

This interdepartmental accessibility is one important reason that MU has become a center of comparative medicine, Stewart says. “NIH saw this development in the number of our publications in top research journals and the ongoing collaborations we enjoy.”

Regional Biocontainment Laboratory staff scientist Deborah Anderson and her husband Paul, who manages the three-story, 30,000-square-foot facility, relocated to MU from Chicago. They made the move in part, they admit, to escape a brutal commute to the biocontainment lab they managed for the University of Chicago. But the same advantages that attracted NIH also appealed to them.

“There’s no question that the comparative medicine program here is unique,” says Deborah Anderson. “Having the veterinary diagnostic lab right next door, for instance, is a real plus.”   

Anderson specializes in Yersinia pestis, the plague bug that nearly wiped out Europe during the Middle Ages. Her work is an example of the types of pathogens researchers at the facility will be working to defeat.

Once known as Black Death, bubonic plague is a flea-transmitted Yersinia pestis infection that swells patients’ lymph nodes into “buboes.” It has claimed nearly 200 million lives in several major pandemics over the centuries. Some of these deaths resulted from the very sorts of terror tactics the MU biocontainment lab is meant to deter. The Imperial Japanese Army, for example, used Y. pestis during the second Sino-Japanese War in 1940, releasing infected fleas over Chinese soldiers. Pneumonic plague is a lesser-known but more virulent form of the Y. pestis lung infection.

Anderson and her team are investigating how Y. pestis builds its own tiny “injection needle” to shoot the host full of proteins called “virulence factors” that kill immune cells and pave the way for Yersinia to undergo rapid replication.  

Using bacterial genetics, “we’re working to develop vaccines and treatments that prevent plague by blocking the movement of virulence factors into host cells,” she explains.    

Walking into her soon-to-be-operational laboratory, Anderson points out that the most complex part of her work involves the painstaking care with which she handles the tools of her trade.

“With a microscope, centrifuge, incubator, and Yersinia cultures in liquid form, I’m pretty much in business,” she explains. “One of my first projects here at RBL will be to create an artificial mutation that changes or deletes the genes that help Yersinia infect a host.” 

After a pending Centers for Disease Control inspection, the lab will “go hot,” Anderson says, triggering a series of worker safeguards that include mandatory showers, and for those who wear eyeglasses, multiple pairs — one for life outside the lab and one for work within.  

Negatively pressurized air, she says, will keep “everything inside,” while fume hoods connected to multi-layered high-efficiency particulate, or HEPA, filters will guarantee that not even the smallest bio-particle escapes its research confines.

As for the lab space, “everything is routinely disinfected with hydrogen peroxide,” Stewart explains. “And my personal favorite,” Anderson adds.  “Good old Clorox bleach.”  

Staying Secure 

“I think they look like little Christmas lights,” says George Stewart, reflecting on the blues and greens of chemically fluoresced anthrax spores that sparkle in a photomicrograph. 

The veterinary pathobiologist has devoted his career to understanding how Bacillus anthracis uses a protective coating — the spore — to survive harsh conditions, travel, and infect new hosts.  Their bright, cheery colors belying a deadly potential, the fluorescent tags help track and identify the spores. 

“The spore represents the infectious form of anthrax, which lives in the soil,” Stewart explains. “I study its outermost part to find out how it initiates infection.” 

No better example of bioterror may exist than anthrax, which exploded onto the American psyche shortly after the September 11 attacks.  Ironically, the offending spores may have come from a national bio-defense laboratory, disseminated through the U. S. mail to high-ranking targets in government and business. 

One need look no farther than the anthrax attacks to realize that bioterrorism is all about dissemination, says Saint Louis University infectious disease specialist Terri Rebmann. 

“Infect cattle, spread droplets in the air, send spores in the mail: The number of ways a bioterrorist can attack is almost endless,” explains Rebmann, an MU nursing school graduate who specializes in infectious diseases at Saint Louis University’s Institute for Biosecurity.

Combating bioterror likewise hinges on learning how microscopic pathogens “stay viable” during the dissemination process — one of many reasons “MU’s biocontainment laboratory is an essential component in the national security framework,” Rebmann explains. 
 
Anthrax stays viable using the spore, which is mostly a “protective protein coat,” Stewart says. Although a vaccine exists for the disease, genetic research at RBL presents additional opportunities. 

A bacterial geneticist by training, Stewart is interested in "making mutants that will help make a better anthrax vaccine.” 

Safety in Redundancy 

"Redundant" doesn’t sound like a word most people would consider complimentary. But to RBL facilities director Paul Anderson, there is no higher praise.

“We have 30,000 total square feet here, but we only use 10,000 square feet for lab space,” he explains. “There’s a good reason for that.”

That reason, Anderson shows, involves the 20,000 or so square feet devoted to "redundant systems:" layer after protective layer designed to keep the RBL’s deadly charges thoroughly contained. “We have not just one, but three air handling systems,” Anderson says.  “And not only do we have a backup generator if the power shuts down, but a backup battery to keep things humming until the generator kicks on.” 

The extra square footage also means maintenance and engineering personnel don’t have to worry about containment outside the laboratories.  Designed to make routine tasks more accessible, the containment bubble protects only the labs. 

But that doesn’t mean just anyone can enter the building.  Even "first responders" from police and fire departments must be escorted.  And no one comes in alone. “Even lab researchers work in pairs,” Anderson explains. “It’s another failsafe to make sure nothing goes wrong.”  

Entering his wife’s soon-to-be lab, Anderson waits until a monitor indicates that pressure is equalized between hallway and room. An electromagnetic lock relinquishes its grip on a rubber-sealed door with a soft click.  The magnetic locks throughout the building open no door before its time, Anderson explains. “They operate in sequence, so we never break containment.”

A built-in autoclave that disinfects everything from tools to clothes illustrates the facility’s interconnectedness. The autoclave has its own boiler, one of several in the basement that generate steam to keep building systems comfortably warm for humans, but deadly hot for pathogens.

In a basement room just beyond two large Culligan water softeners, MU building systems engineer Tom Bland spends several hours every week adjusting pH, testing thermostats, and keeping watch over a pair of big blue boilers from the family-owned Hurst Company in Coolidge, Georgia.  

“You can’t rush a boiler,” says Bland, who enjoys maintaining these sometimes-temperamental giants. “I can relate to that.”

For economic-development types who track domestic employment impacts from projects like the RBL, the boilers, heat boxes, gauges, and other brand new building systems should be a comforting sight. To Bland, they mostly represent new challenges in the high-security, ultra-clean laboratory environment. “NIH hosted a week-long facility engineering course so that we would know exactly what to expect and how to operate in this setting,” he says. 

Knowing lab employees receive specialized training comforts Columbia city councilman Karl Skala, who recently retired from the Swine Research Center as a physiologist and laboratory manager. “You can have all the redundant systems in the world, but you have to address the potential for human error,” said Skala, who recently toured the RBL. “What I saw impressed me, and I’m glad the extra precautions are in place.”

Dangerous, But Curable 

HIV— the Human Immunodeficiency Virus — causes AIDS in monkeys and humans, but it’s not on RBL’s pathogen study list because it’s incurable, at least presently, a key distinction in the security hierarchy of the nation’s biocontainment facilities. “We’re a Level 3 lab, which means we only deal with pathogens and diseases that have known cures,” Stewart says. 

The distinction also explains why there hasn’t been much hoopla surrounding RBL. In 2006, some Columbia residents protested a proposed biocontainment laboratory designed to replace the Animal Disease Center in Plum Island, N.Y. That lab was a Level 4 homeland security operation, Stewart explains. “And Level 4 labs only deal with diseases and germs for which there is no cure, like Ebola.” 

The RBL is different. “We’re currently NIH-funded and operated by the University,” Stewart says. “We have little to do with Homeland Security.”

Terri Rebmann, who last year placed a student intern at the U. S. Army Medical Research Institute for Infectious Diseases, a Level 4 lab, says she’s glad the RBL is so close to St. Louis. As chair of the emergency preparedness committee of the Association of Professionals in Infection Control, Rebmann says, “my focus is on disaster preparedness for hospitals, health departments, and other emergency responders. So having a lab of this caliber nearby for possible collaborations is nothing short of wonderful.”  

The RBL is a non-descript building at the end of a short gravel drive. It’s hard to imagine that such an architecturally unassuming structure will shortly become home to some of the world’s most impressive engines of innovation. From a distance, in fact, the laboratory looks almost like a simple Amish barn. To Stewart, that’s all part of what makes it a unique research environment. 

“I’ve always liked the architecture, even on sketches and drawings,” he says. “It’s very down to earth and very real.”