by Rebecca Kolberg

Improving safety and improving ease of scientific research are not necessarily mutually exclusive. Proof of that has just arrived on the south edge of the NIH campus in the form of a newly renovated facility for research involving pathogens that demand the highest levels of containment.

Although the new Maximum Containment Laboratory (MCL) is located in the same space as NIH's old Biosafety Level-4 (BL-4) facility in Building 41A, the difference between the old and new facilities extends far beyond a simple name change. Gone is the old "glovebox" approach, in which walls separated researchers from pathogens, forcing them to manipulate pathogen-exposed animals, samples, and equipment through bulky gloves inserted in fixed portholes. Inside MCL, researchers clad in plastic astronaut-like suits, with their own spiral breathing tubes hooked up to an outside air source, will be able to move about in relative freedom and conduct scientific and animal-care procedures more like they would in a normal lab.

Maximum Containment Lab

"We built MCL with flexibility in mind-although it may seem like an oxymoron to mention BL-4 containment in the same breath as flexibility," says Deborah Wilson, chief of the Occupational Safety and Health Branch in NIH's Division of Safety.

When it is completed later this summer, the $3.6 million MCL will be one of only three "suit-system" BL-4 research units in the United States. The others are at the Centers for Disease Control and Prevention in Atlanta and at the U.S. Army Medical Research Institute for Infectious Disease in Fort Detrick, Md. NIH expects that both intramural and extramural researchers will use MCL and has set up the MCL Program Review Committee to examine proposals for scientific merit and safety concerns.

NIH's previous BL-4 facility, established in the mid-1970s for research involving recombinant DNA and cancer-causing viruses, later housed NIAID scientist Malcolm Martin's transgenic mouse containing the entire genome of the human immunodeficiency virus. But the old facility's design limited the types of benchwork that could be undertaken with pathogens requiring maximum levels of containment and could only handle animal projects involving small rodents. The new facility, with three interchangeable modules of lab and animal-care space, can accommodate animals ranging in size from mice to nonhuman primates.

According to Wilson, the emphasis on freedom of movement should make work safer for researchers in MCL. The old facility's cramped and inflexible glovebox design often led to researcher fatigue and made it difficult to maneuver sharp instruments during surgery and other procedures. Like BL-4, MCL will be limited to research on just one pathogen at any given time. However, the increased workspace of the new facility-about 2,000 square feet compared with the previous glovebox space of less than 500 square feet-should make it easier to simultaneously conduct a variety of studies involving the same pathogen than it has been in the past, Wilson says.

Mycobacterium tuberculosis will be the focus of the first research project in MCL: a series of NIAID studies aimed at creating a suitable animal model to use in testing therapeutic and vaccine interventions against multi-drug-resistant tuberculosis (MDR TB). Although M. tuberculosis itself is not a BL-4 pathogen, the MCL Program Review Committee agreed that maximum containment was indicated for such studies because the strains to be used in the studies are multi-drug resistant and because the inoculum will be delivered by aerosol-the route by which most TB infections are acquired.

On the basis of past work describing the pathogenesis of TB in rabbits, NIAID's Mark Simpson, Thomas Kindt, and Richard G. Wyatt plan to explore the possibility of using rabbits as models for MDR TB. Among those assisting the NIAID team with the study will be the Division of Safety's Wilson, a microbiologist whose doctoral research was on the effect of vaccination on guinea pigs that were infected with M. tuberculosis through the aerosol route. Because the researchers want to familiarize themselves with the new facility and because the pathogenesis of MDR and non-MDR TB do not apparently differ, the initial study will be done with non-MDR TB. However, MDR strains will play an important role in future studies that will analyze interventions.

"The design of the old facility would not have permitted the study of rabbits. Technology has advanced since that facility opened, and the new facility will take advantage of that new technology," says Wyatt. "The Division of Safety did a superb job in designing the space."

Although researchers who use MCL will pay for supplies and animals used in their experiments, the Office of Research Services will cover the actual cost of running MCL. A major expense for researchers using MCL will likely be the labor costs involved in training people to work in the state-of-the-art facility. Wilson estimates that most staff will require at least a couple weeks of special safety training, including performing dry runs of their experiments, before receiving the go-ahead to begin their research with a BL-4 pathogen.

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