Designing a 'Hot Zone'

Photo courtesy of NIAID/NIH When Tulane's new BSL-3 lab opens at its national primate center in Covington, researchers will be required to wear protective gear that guards workers from potential hazards. This photo was taken at another of the country's BSL-3 labs.

It's a chilly day, and Robert Johnson, communications director for the Tulane National Primate Research Center, leads a small tour of the newest facility at the center's Covington complex. The afternoon sun glints off the modern steel-and-glass structure. A dozen workers buzz in and out of the building, carrying spools of wire and tubs of epoxy.

"Watch your step," Johnson says over the whir of a drill. "And watch your head."

Everyone in the group has been outfitted with a hard hat and strict instructions to take no photographs. The nearly finished work-in-progress is a biosafety level 3 laboratory (BSL3), and security is important. The building is the future site of research into vaccines and therapies for federally regulated infectious diseases like tuberculosis, plague and typhus.

After two years and $27.5 million in construction, the lab is one of 13 Regional Biosafety Labs (RBLs) scattered across the country. Heavily subsidized by the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID), the RBL network is part of the National Biodefense Program developed in the wake of the anthrax scare of 2001. It is an infrastructure of intellectual and physical capital designed to protect the public from biological threats — naturally occurring and otherwise.

This tour is a rare opportunity to peek inside a BSL3 before it is commissioned. After the building's ribbon cutting on Dec. 5, the lab will close to everyone but the scientists and technicians who work there.

Standing at the doorway to the complex, the space smells of new asphalt and fresh paint. Soon, there will be no such smell — soon, the air inside will be so clean, so perfectly filtered, that, according to the director of the center, people who suffer from seasonal allergies will find respite working there.

That is, of course, if they make it past the front door.

"You're at more risk driving from here to New Orleans than you are working in the lab," says Dr. Andrew Lackner, director of the Primate Research Center.

He quickly rattles off a score of security measures that occur even before the research begins in the RBL. A career scientist specializing in veterinary medicine and emerging infectious diseases, Lackner is acutely aware of how safe the lab actually is versus public perception of lab safety. After all, labs like this are a favorite template for Hollywood thrillers (Outbreak) and horror movies (I Am Legend and the 28-Time-Units-Later franchise).

"The first thing to remember is that we know exactly what we're working with when we're working with it, as opposed to, say, somebody walking into a hospital in New Orleans off of a plane with a fever," Lackner says. "(In that case) it could be a common cold, it could be anything. In our case, we know what we have."

Employees at the center are already intimately familiar with level 3 labs and protocols for nonhuman primate (monkey) trials. The center's facilities have included a BSL3 for more than 20 years, and the center is certified to work with "select agents" — the euphemism for federally regulated bacterial, viral and toxic pathogens. The center's breeding colonies of more than 4,000 monkeys have long made it an attractive resource for researchers studying models of diseases and therapeutics in primates. In fact, many of the first projects that will be run through the new RBL will be transferred from the old lab.

"Biodefense is essentially making vaccines, diagnostics, therapeutics against infectious agents," Lackner says, stressing the lab will not be a weapons factory. "Those terms often get used synonymously — and they are anything but — with bioterror, bioweapons and biowarfare. ... Those are things that are designed to hurt people."

Before any researchers can even get to the front door of the lab, they are vetted through a multifaceted security screening. Anyone who needs to work with the select agents must first be fingerprinted and pass a Department of Justice background check — on top of the criminal background check and academic degree verification required of all Tulane employees in these positions. Researchers then undergo a health exam to ensure they are not ill and can safely wear the necessary protective equipment.

An architectural rendering of the BSL-3 lab facility, scheduled to open soon at the Tulane National Primate Center in Covington.

Researchers also must have a substantial NIH grant to be considered for a spot in the new lab. The granting process is its own informal screening mechanism. Any proposals to the NIH are peer-reviewed and assessed on the basis of the study's ethical, technical and potential scientific merits. Only one in 10 investigators who apply for these kinds of NIH grants win funding. Investigators then compete for lab space. The RBL will create 60 new jobs, including animal handler and lab technician support positions.

"There are people backed up at the door now. ... NIH investigators with funded grants," Lackner says.

One of the researchers who already earned real estate in the new RBL is Dr. Chad Roy, a microbiology faculty member at the center and the Tulane School of Medicine. The aerobiologist — someone who studies how pathogens are transmitted through the air — will continue to work on studies he started in the old BSL3 as well as a vaccine study of Eastern equine encephalitis.

"It's an absolutely phenomenal resource," Roy says. "The nonhuman primate provides an ideal model to study the disease." He's excited about the upgraded features of the new RBL — not the least of which is breathing room. The facility is almost 39,000 square feet, and nearly half of that is lab space. There are also posh offices at the building's entrance.

Roy has worked with bacteria and viruses in level 3 and level 4 labs across the country — including the United States Army Medical Research Institute for Infectious Diseases (USAMRIID), made famous in Richard Preston's bookss The Hot Zone and The Demon in the Freezer — and prefers level 3 labs like the RBL.

"In level 4 you're wearing one of the big blue suits you see in the movies," he says. The cumbersome gear limits mobility, and dressing out of the space suits is a necessarily time-consuming process because the viruses studied in BSL4 labs are largely fatal and incurable. (In the BSL3 labs, like Tulane's RBL, there are vaccines and antibiotics that work for the majority of the pathogens studied.) "BSL4 is a pain in the butt to work in and that's why I don't work there," Roy says.

Not that the investigators at the RBL in Covington won't be wearing serious personal protective equipment. After entering the offices of the RBL, researchers headed for the "wet labs" where live agents and pathogens will be present will change into scrubs. They will then enter an antechamber where they suit up in positive-pressure, full-head respirators, so if a leak develops in the mask, air will rush out of the respirator, limiting the chance for contamination. Everyone inside the lab wears two sets of latex gloves, and nothing worn inside the "dirty areas" ever leaves the lab.

The whole building is a fortress designed so nothing exposed to contaminants leaves the lab. Air entering and exiting the lab is HEPA filtered to remove all particulate matter. The interior surfaces are coated with a special epoxy paint that keeps bacteria from sticking to the walls and ceiling. The doors are hung on continuous hinges that prevent leakage between rooms. All waste from the lab is processed through a high-pressure chemical digester, obliterating any trace of organic matter.

Like the theory behind the headgear, the building is maintained at negative pressure so if it were structurally damaged, air would rush into the building instead of out of it. The likelihood of that ever happening is small; the structure stands on piles that go approximately 80 feet into the ground and it is designed to withstand winds up to 350 mph.

Then there are the redundancies: multiple HEPA filters, multiple backup-generators and multiple cameras in every lab space. Before any researchers set up shop in the lab, every system will undergo testing.

"There will be a 21-day test where the building is up and running," says Jesse Shurtz, the general superintendent for Gilbane Inc., the construction company building the RBL. "You cause calculated failures on some of the systems to make sure that it recovers and it operates properly."

Even personnel security has built-in redundancies. "I thought they were joking when they said, 'retinal scans,'" Roy says. They were not. Along with special identification cards, lab workers will have to pass eye scans to enter the labs.

The RBL ribbon cutting coincides with the Tulane University 2008 Presidential Symposium: "Emerging Infectious Diseases and Global Risk." Representatives from the NIH and possibly Gov. Bobby Jindal will be on hand to christen the building. The ceremony will be an invitation-only affair, though a lecture by John Barry, author of The Great Influenza: The Epic Story of the Deadliest Plague in History, will be open to the public the night before, on Dec. 4.

Even though the primate center has had a BSL3 for more than 20 years, a new facility like the RBL adds huge cachet to the institution. "It's the same science," Roy says, "but you know everybody likes to have nice digs to work in."