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Starting from Scratch

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Let's say you won a grant worth $140,000. What would you do with it? Chances are, parlaying that funding into your own fledgling research institute would be pretty far from your mind.

But that's just what Ken Stuart did in 1976, when he was in his mid-30s and received his first NIH grant. It was a modest, two-year award at $37,000 per year (adjusted for inflation, that's worth about $140,000 today). He used the money to rent space in an office park, start up his research lab focusing on global infectious disease, and pay his salary. It was a humble beginning for the Seattle Biomedical Research Institute.

Stuart says that his early training experiences had provided examples, both good and bad, of different types of research environments. A stint at the National Institute for Medical Research just outside London showed him an institution that "enhanced the ability of scientists to conduct research," while a teaching gig at a Florida university made clear the distracting duties of teaching and other administrative necessities. His vision was simple: to create a "research environment that was efficient and effective" — a place where research was first and foremost, and any other tasks were kept to a minimum.

Stuart's gamble paid off: "People were attracted by the environment that I'd created," he says, and over the next decade the institute came to be known as a place to do intensive science. But with that emphasis on science came a lack of overall goals for the institute as a whole. "The way the institute developed, it really was sort of a collection of independent laboratories," he says. By the '90s, Stuart had become interested in pursuing infectious disease research beyond the basic lab and wanted to focus on translational work. Internal discussions over time revolved around whether to remain as a series of "boutique laboratories," says Stuart, or to make the transition to "a full-fledged research institute with an integrated vision and mission." They made the transition.

In early 2004, SBRI moved into a new $40 million facility, built after a major fundraising effort. Today, the institute occupies some of the space and leases out the rest to researchers from a local children's hospital as well as some companies. Stuart says that he expects the institute, which has been growing at about 25 percent annually for the past five years, to eventually take over the entire building. Today, SBRI boasts a staff of 260 with 15 principal investigators; Stuart plans to increase that over time to 400 full-time employees.

Need for translation

While getting scientists to buy into the vision of one institute instead of many labs might have taken some discussions, Stuart says the real challenge in the course of the group's development has been getting people to embrace translational research. At the very beginning of the institute, this wasn't even an option, he says. In the mid-'70s, studies on infectious disease were so early-stage that "I could not really see a way to do research that would support the activities that would lead to interventions," Stuart recalls.

But in the past decade or so, that has changed radically, especially in the areas that SBRI scientists focus on: HIV, tuberculosis, malaria, and emerging infectious disease. The real problem was that the public funding system "didn't reward" translational work, Stuart says; scientists are rewarded for basic research and for publishing. "We had many discussions about [working toward an intervention] — why that's strategically important, why it's morally important."

Today, SBRI scientists are months away from clinical trials for a malaria vaccine, and they have other promising candidates for HIV and malaria in the pipeline. The first one, which is expected to enter trials in 12 to 18 months, began with work by malaria expert Stefan Kappe, who joined the institute five years ago. He says a significant lure of SBRI was that as an independent institution — rather than, say, a program within a medical school — it's "very nimble" and "we can shift our priorities very rapidly."

Kappe knew that working toward a vaccine was part of the goal of the malaria program, so he focused his research on the liver stage of the parasite, which is when it enters its human host but remains undetected for seven days before spreading out into the bloodstream and causing infection. Using functional genomic studies and mouse models, Kappe and his team were able to determine the gene expression pattern during this stage for the first time. Knockout studies proved that deleting certain genes at this stage left the parasite unable to complete its life cycle and infect the host. In mouse models, dosing the mice with this genetically engineered version of malaria induced a "very powerful protective immune response" — such that when the mice were then infected with full-strength malaria, the mice proved to be completely immune over the course of their lifetime. During the upcoming clinical trials, the same process will be performed on human patients to see if the immune response holds true.

Another potential malaria vaccine comes from Patrick Duffy's group, which is studying pregnancy malaria. The team has identified a key protein used by parasites in the placenta, and are aiming to develop a vaccine to target the protein.

Going global

As he was getting the institute going, Stuart realized that his group would never be large enough to have expertise in all areas of infectious disease — so collaborations have been essential to SBRI's development. Currently, for instance, many of the partnerships help the institute connect with people who are experts in developing vaccines. The institute's website lists 125 collaborations with partners ranging from New York University to Novartis to the University of Nairobi. "From our total budget," Stuart says — this year, that's $40 million — "about half of it goes out the door to support our collaborative activities."

Seattle Biomedical Research Institute

Seattle, Wash.
Director: Ken Stuart
Established: 1976
Size: In March 2004, the SBRI team moved into a new $40 million, five-story facility. The institute currently leases out space to researchers from Children's Hospital & Regional Medical Center and to companies, but planned expansions to the staff will likely have the institute take over the whole building in the future.

Staff: During the past five years, SBRI has been growing at about 25 percent annually, bringing its headcount to 260 employees (not all of whom are full-time). The institute plans to increase that to 400 full-time employees. There are 15 PIs on staff.
Funding: The institute's current annual budget is $40 million, almost all of which comes from grant funding, though the SBRI team has begun to focus more on fundraising with philanthropic organizations.
Focus: The main program areas are HIV, malaria, tuberculosis, and emerging infectious disease.
Core labs: SBRI's cores include technologies for DNA sequencing, imaging, protein production, proteomics, bioinformatics, and more.
Collaborators: SBRI places a strong emphasis on partnerships with other institutions to help extend its reach and capabilities. The group has more than 100 alliances, with partners including Microsoft, Harvard, Walter Reed Army Institute of Research, the Pasteur Institute, and Novartis, to name a few.

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