Finding suitable lab space for U.S. scientists to conduct human embryonic stem cell research has been tricky business. University of California, San Francisco researchers in 2001 had to rent lab space off campus to derive what were believed to be the first new lines nourished in a cell culture on a bed of human cells. This made them superior to previous lines, which had been contaminated by the layer of mouse cells used to culture them. Bush Administration regulations prohibiting scientists from deriving new human embryonic stem cell lines in facilities where federally funded research is performed had forced such lab relocations.

 

Everything was going just fine in the new digs until a major storm hit the Bay Area in 2002, causing power outages that left the space without electricity for days. Unable to bring the cells back to UCSF where back-up generators were keeping the lights on, researchers had to let the cells die. The loss set the lab’s work back nearly two years, says Susan Fisher, the lead researcher on the project.

 

After the setback, researchers moved again, this time to a lab at stem cell therapeutics pioneer Geron, which had been one of the study’s funders. But at about 30 miles south of UCSF, the location in Menlo Park, California was less than ideal. “The commuting was a major strain on the researchers, says Dr. Arnold Kriegstein, director of the UCSF Institute for Regeneration Medicine.

 

Thanks to California’s $3-billion stem cell research initiative passed by voters in 2004, this bouncing from place to place will be drawing to a close. UCSF is one of 12 institutions statewide receiving a chunk of the $831 million raised through Proposition 71 and other donations to build stem cell research facilities free of the federal restrictions. As undifferentiated cells that can develop into many different cell types in the body, stem cells are being looked at as a potential source of new treatments for the world’s most fearsome ailments including cancer, Alzheimer’s, and diabetes, among many others. The heat is on as California’s stem cell push involves building some 800,000 square feet of research space in two years so that more than 1,000 top scientists and support staff can move in by mid 2010.

 

“The challenge is to develop in such a short timeframe the capacity that is at the level that is really needed to get these new medicines,” says Dr. Alan Trounson, president of the California Institute for Regenerative Medicine or CIRM, which is the state’s stem cell agency formed by the ballot initiative. “It has required us to put together in these facilities all the components of the pipeline.” Those include basic research, then the work that “translates” that research into real therapies, and finally, the clinical research that actually tests those therapies. “The important thing is that the discovery travels along the pipeline and doesn’t just stay a good idea that is never developed,” he says.

 

The agency announced its facility awards on May 7, about a year after the California Supreme Court dismissed a legal challenge to Prop 71. Even though Trounson and his colleagues at the agency call the timetable “expedited,” they won’t be cutting anyone slack on the two-year completion deadline.

 

In addition to UCSF, six other institutions are essentially constructing stand-alone buildings, including University of California campuses in Irvine, Davis, and San Diego, as well as Stanford University, the University of Southern California, and the Buck Institute for Age Research. UC campuses at Berkeley, Merced, Santa Cruz, Santa Barbara, and Los Angeles will incorporate stem cell research facilities into new or existing buildings. But all will face penalties if they fall behind in construction. “There are real incentives to get this done,” says Trounson.

 

The rather feverish timeline doesn’t mean care and consideration haven’t been put into the design of the buildings. In fact, several have been designed by award-winning architects and are on the cutting edge of laboratory design, considered among the most challenging because of the many technical considerations. “These are incredibly good designs,” says Trounson. The $200-million Stanford Institutes of Medicine 1 will bring researchers, now scattered across campus and beyond, together under a single roof. The 200,000-square feet facility will have 60 “hotel” benches for collaborating scientists both on and off campus and is designed to use up to 30 percent less energy than a comparable research building.

 

Down in Southern California, the $82.6-million Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC—named after the Los Angeles philanthropists who donated a combined $50 million to stem cell research efforts at USC and UCLA—was designed by Zimmer Gunsul Frasca Architects. The five-story, 87,537-square-foot facility gets rave reviews from the magazine AIArchitect, which says “glass and granite come together to create a model of practical sustainability and efficiency.”

 

The building least likely to win the dowdy award, however, is UCSF’s $119-million building designed by renowned New York architect Rafael Viñoly. Shaped in a gentle curve—just like the tilde over the Uruguayan-born architect’s last name—the building’s 74,000-square feet stretch over a series of split-level floors and terraced outdoor green spaces. Mindful of a study concluding people are likely to travel 10 times farther horizontally than they are vertically, the architect designed each floor to be only a half flight of stairs to the next floor so that scientists can easily see from one lab to the next.

 

“There is a visual continuity from floor to floor,” says UCSF’s Kriegstein. “You will never feel isolated. There is a kind of seamless connection between the different spaces.”

The easy flow was intended to foster collaboration as, UCSF notes, scientists looking to generate insulin-producing beta cells, for instance, will be based near researchers trying to develop nerve cells “because stem cells undergo nearly identical molecular signaling on the path to becoming both cell types.” Overall, some 25 principal investigators will be based in the building along with other support staff, bringing the total to about 250, says Kriegstein.

 

They’ll each be working on one of nine pipelines centered on different body systems such as the nervous system or the cardiovascular system. “The overarching goal is to develop stem cell replacement therapies,” says Kriegstein, adding that this includes replacing injured or damaged organs with ones developed through a stem cell source. “That’s a tall order,” he says. Projects such as replacing the beta cells lost in type 1 diabetes with new insulin-producing ones created through stem cells may be more doable than others, he says. And stem cells’ pluripotency—their ability to turn into different cells—could be exploited not just for replacement therapies but also for testing the safety or side-effects of new drugs, he adds. Creating heart muscle cells, say, in a dish, could allow scientists to investigate potential problems or cardiac side effects of drugs before conducting human clinical trials, he says.

 

Setting up in the new building will end what Kriegstein calls the “nightmare of accounting” that requires scientists to perform any non-federally approved stem cell research with space and equipment separate from that used for federally funded research. The mandate has been a hassle since much of university biomedical research is federally funded.

 

In 2001, the Bush Administration said there would only be federal funding for the human embryonic stem cell lines that had already been produced from surplus embryos from in-vitro fertilization at the time of the announcement seven years ago. Deriving new human embryonic stem cells requires researchers to destroy human embryos, which is the main reason the administration has imposed the restrictions. The restrictions, however, didn’t ban human embryonic stem cell research from private—or in California’s case, public—sources. Still, the National Institutes of Health registry lists only 21 lines eligible for use, forcing scientists who want to work with newer and more pristine lines to keep their workspaces and equipment separate from those linked to NIH-funded work. “If there is an active NIH grant in the lab, you can’t even use a microscope for non-designated work,” says Kriegstein. “It will be easier to perform research in the space of the new building.”

 

That’s the same feeling down at the San Diego Consortium for Regenerative Medicine, where the $115-million research facility on Torrey Pines mesa will have a demanding task: housing scientists from four different institutions. The “SDCIRM” consortium is comprised of the University of California, San Diego, the Burnham Institute for Medical Research, the Salk Institute for Biological Studies, and the Scripps Research Institute.

But Louis Coffman, the consortium’s vice president, says the 135,000-square foot building, designed by Jeff Olson of Denver-based Fentress Architects, is up to the challenge. The four-story building’s emphasis is on being functional and flexible, since it can comfortably accommodate no more than 30 resident scientists among the 160-odd researchers doing stem cell-related work at the four institutions, he says. All the casework is moveable so that gas, water, and power hookups, for example, are connected to pods in the ceilings and can be easily switched around as needs change. The building’s net-to-gross, or the amount of useable space excluding mechanical and other non-assignable areas, is 70 percent, while most buildings are closer to 60 percent, he says. “We really believe we put a lot of function in there,” Coffman says.

 

The “collaboratory,” as the consortium likes to call the facility, will have many conference and meeting rooms to encourage scientists to share information and expertise. Key research focuses, Coffman says, will include developing new tools and diagnostics to treat various diseases, as well as recruiting and training the next-generation of neuroscientists. What’s more, the building is designed to conserve and recycle water as well as use lots of natural ventilation and light—all with the goal of obtaining LEED Gold certification, a high mark in green building. For those who aren’t cycling to work, Coffman says there will also be ample parking, some 320 spaces for the 300 who work in the building. “People can dread going to work when there isn’t enough parking,” he says.

 

Indeed, getting employees to come to work in any of these new facilities shouldn’t be tough, says Trounson. With $530 million in research and facility grants given out to date, CIRM is the world’s biggest source of funding for human embryonic stem cell research. A recent international survey of scientists suggests some 90 percent would chose to be in California in the area of regenerative medicine, he says. “Most of the scientists I know really have a desire to be here at least part time if not full time,” he says. Note to contractors: best plan for big mailrooms to accommodate all the curricula vitae that will likely be dropping through the slots.