The 74,000-gsf project encompasses two below-grade levels, topped by a 7-1/2-foot-high interstitial level, also underground. Designed to serve researchers at the school's Faculty of Arts and Sciences (FAS), it will offer 18 procedure rooms and 50 holding rooms containing both single-sided and double-sided ventilated racks for micro-isolated cages. About 30,000 of the cages will be available for assignment to principal investigators for general holding, with the remainder to be used for quarantine, core facility holding, and future expansion into shelled space.

"In 1998, we had two aging animal facilities, one barrier and one conventional, with a combined count of approximately 4,300 cages—not enough to support the existing faculty at the time," says Sharalee Field, senior planner for the sciences at Harvard FAS. "With future recruitment plans, plus the increasing interest generated by the transgenic core, and growing interest from other faculty members who were formerly not major mouse users, including some from the chemistry department, we felt this new facility would permanently handle our expansion needs a decade out from the time of construction."

Why Underground?

While Field allows that it might have been less complicated to build a small above-grade vivarium elsewhere on campus, the underground scheme actually offers several benefits, not the least of which is that it will keep the facility as secure and as low-key as possible.

"Putting the facility completely underground, out of sight, out of mind, is a good way to meet these goals," she comments. "We also anticipate that it will be easier to maintain temperature and humidity control in a subterranean box that is quite well insulated with dirt on all sides."

However, below-grade construction with a slurry wall is expensive, and costs rise with every foot of depth. Field and her team explored the option of a one-story underground building, but determined that, in light of the high fixed cost of the cage wash and other support areas, the per-cage cost of a smaller, single-level facility would be prohibitive.

The final design represents a compromise, with the interstitial space limited to the level over the main holding rooms, LL1. The interstitial area has a walk-on floor only above the corridors of the floor below, with mechanical equipment installed above the holding and procedure rooms. Access is provided from both the freight elevator and stairwells at either end.

LL1 has a height of nine feet clear from the top of the floor slab to the underside of its finished ceiling. The floor below, LL2, houses the mechanical area, quarantine, and cage wash in a space 15 feet high from the top of the floor slab to the underside of the LL1 slab.

"Eliminating the interstitial floor above LL2 was a challenge for our MEP engineers, Bard, Rao + Athanas, but they managed to fit everything necessary in the limited space," Field notes.

She also points out that the cost of digging 50 feet below ground level has been at least partially offset by not having to provide a decorative building exterior.

"Fancy curtainwalls can be quite expensive, and the mice don't need windows, so this seemed to be a perfect fit," she quips, adding,"For an institution like Harvard, every square foot of land is precious. We have no expansion room, so conserving land and simultaneously preserving our open spaces is a win-win situation."

Hurdles

In addition to a constrained site, one of the early hurdles Harvard had to overcome was providing for the huge volume of air that would be entering and exiting the below-grade facility. For supply air, the solution was relatively simple: concealing the intakes in the ground-level landscape. The need for an elevated exhaust stack was more challenging. Ultimately, Tsoi Kobus & Associates, the project architect, devised a ten-by-ten-foot exhaust shaft running up to the roof of an adjacent building, cleverly integrated with that building's historic façade.

Another snag arose when the state water management resources agency nixed Harvard's plan to dispose of dirty cage waste via a Gar-bel, a machine like a giant garbage disposal that would have been integrated with the tunnel washer to grind the damp solid matter into a slurry mixture to be discharged into the sanitary sewer.

Despite the fact that a handful of such disposal mechanisms were operational in other Cambridge facilities, the agency decided that a study of the impact on the regional sewer system was necessary before granting additional approvals.

Going back to the drawing board, the design team produced a pneumatic system that pipes the waste from the tunnel washer line to sealed dumpsters on the loading dock.

Redundancies

Given the value of the mouse colonies that the building will house, redundancy provisions for the BRI received significant attention.

Along with back-up generators for critical electrical loads and an extra (fourth) Strobic fan to handle exhaust at the roof level, in the event of a power outage or malfunction heat and cooling power from the University's central steam and chilled water plants can be replaced by a supplier who will bring in temporary boilers and chillers on a flatbed truck.

"Planning for this meant we had to bring the connections for the temporary chilled water and the temporary steam above grade to a location where we can park three trucks side by side— chiller truck, a steam truck, and a fuel truck to service them," Field explains.

Redundancy on the cage-wash side was especially important in light of the BRI's dependence on automated tunnel washers with gantry robots at both ends to deposit and remove cages. Harvard opted to have two tunnel washers operating from day one instead of postponing the installation of a second unit to the future. Should one machine or the gantry robots go down, cages can still be run through one of the washers manually while repairs are being made. Similarly, the number of bulk autoclaves in the main cage-wash area was boosted from two to three, which will help maintain an eight to ten-hour ideal cycle time when the facility is ultimately equipped with all 40,000 cages.

"In the meantime, this arrangement gives us the redundancy of always having two operational autoclaves if one should go down," says Field, observing, "We all live with the nightmare scenario that one major facilities-related crisis could wipe out years of research, possibly destroying work done by the PI who would have cured cancer. We had to walk a fine line between giving in to our paranoia by installing two sets of everything and doing what we basically thought was prudent."

A substantial under-slab drainage system and a perimeter drainage system have been constructed around the facility to handle flooding that might result from a sudden rainstorm. Fortunately, New England isn't typically subject to the types of flash flooding that plague other geographic areas, Field points out.

Future Flexibility

Looking ahead, Harvard decided to make provisions within the vivarium for BSL-3 capability, designating a corner of the current quarantine suite as the location of the future facility, should it ever be required. Preliminary preparation entailed installing the required dedicated stainless steel exhaust duct up to the roof level of an adjacent building, an expensive process.

"It was costly, but if we had deferred the duct to the future, it would basically have been impossible to construct," says Field. "We made the necessary provisions for the entry airlock and exit airlock with an emergency shower for the BSL-3 facility. We also designed the path leading through the decontamination staging area, with a pass-through autoclave that empties out into the dirty side of the cage wash."

A total of 3,200 sf of shell space on the lower level next to the cage wash will accommodate other future needs, whether for an imaging suite or additional species, or for more quarantine space to house animals taken out of the barrier.

New Materials and Products

Floors in the BRI will be covered with a new monolithic, resin-based system called N2 from Seamless Technologies. Very resilient, like epoxy, it has the advantages of an odor-free installation and extremely high durability. Harvard gave the material a trial run in a biology lab, where it withstood even liquid nitrogen spills. In the event it does become damaged, the floor can be easily repaired by in-house personnel using a handheld UV light and a small jar of resin—and no disruptive odor.

In addition to the tunnel washers with robotic arms to load and remove cages, Field's team decided to deploy an automatic watering system. A cost benefit analysis had shown that the automated equipment would pay for itself within six years, also lowering staffing levels and reducing turnover while increasing worker satisfaction.

Still, some 10 to 20 percent of the animals will likely need water bottles, despite the automatic watering system. Plans to address that requirement with an automatic bottle uncapper and capper were eliminated when the hidden cost of adding a third axis to the gantry robot system surfaced. Instead, Harvard explored alternative technologies that produce sterile, disposable bags of water that can be fitted with a nipple and placed on the wire bar lids of the cages. The system ultimately selected, "Sipper Sacks" from Edstrom Industries, integrates directly into the automatic watering system, with one changing station in each holding room being equipped with a bag-filling station.

Holding Area Layout

The main holding area features a pod arrangement stemming off a central corridor. Designed to be shared by two senior researchers, a typical pod contains five animal holding rooms and two procedure rooms.

The holding rooms conform to a 16-1/2' by 21-1/2' module, which allows for six single-sided racks and three double-sided racks with five feet between them. Dual animal transfer stations in each room allow animal husbandry staff and a researcher to work simultaneously without conflict.

Initially, the procedure rooms will be outfitted generically, with one side of the room accommodating a movable procedure table with its own scavenger exhaust overhead, but otherwise left clear for individual PI customization. The other side of the room features a six-foot-long clean bench (laminar flow hood), a fixed bench with storage above and below, and a sink. Other standard furnishings include an additional procedure table for an incubator and a refrigerator/freezer, depending on the needs of the individual PI.

Shared spaces include a small procedure room suitable for performing perfusions in a 100-percent-exhausted biosafety cabinet; a transgenic core for the custom production of transgenic mice; and the behavioral core, a suite of rooms with special features or equipment like water mazes and lights on timers for behavioral studies. Support spaces, such as a break room for staff and researchers, lockers and showers, and storage are also incorporated in LL1.

The construction cost of the project will reach roughly $40 million, exclusive of "soft costs" of approximately $21 million including AE fees, movable equipment, and Harvard-specific internal fees, plus approximately $5 million in deferred equipment and shell-space fit-out.

By Nicole Zaro Stahl