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Ripe for a Breakthrough

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In an age of shrinking grant funding, the Burnham Institute in California has managed to post double-digit revenue growth for six years running. Its secret: collaboration and a good connection to the clinic.

John Reed claims that the Burnham Institute for Medical Research, where he serves as president and CEO, has found success by managing to be in the right place at the right times. But with the success metrics the institute has racked up — for one thing, it's had six consecutive years of double-digit revenue growth, even though some 80 percent of the operating budget comes from a budget-crunched NIH and other federal sources — it seems clear that luck has little to do with it.

Much of the success stems from scientific management that has been remarkably accurate in predicting research trends. A decade ago, the Burnham was focused solely on cancer. Reed, who has been with the institute for 16 years, says that the scientific leadership noticed that "we were bumping into things like anti-death genes [and] killer genes," which seemed to have clear applications in neuroscience. "We started toying with the idea of building some strengths in neuroscience," Reed says, "and it just took off like crazy." Since then, the prescient leaders guiding the institute's scientific development have launched pilot projects and then full centers in stem cell research, infectious disease, and most recently diabetes and obesity as well as children's health. Much of this comes from the five-year scientific plans that help steer the institute, and Reed says that in launching new research centers he and his team look for "conditions [that] may be right to make some breakthroughs."

Burnham's work on stem cells, in fact, was so bleeding-edge that the institute already had some 80 employees working in the nascent field when US President George Bush made his famous declaration limiting human stem cell research. Dealing with the new restrictions hobbled the program for a while, but "now that California has put money into stem cell research we've started getting the wind back in our sails," Reed says. The institute now has more than 100 people working in stem cell research, he adds.

The institute has grown rapidly in recent years — Reed says Burnham has more than doubled its staff size — and part of that includes expanding, for the first time, to other locations. The bionanotech group moved offsite to form a nanotechnology center in Santa Barbara, Calif., and Burnham took advantage of Florida's economic development program for biotech by opening a new facility in Orlando. That center, which focuses on diabetes and obesity research, is expected to employ 300 people within 10 years.

As a result, Burnham is facing new challenges in making sure its scientists collaborate and make full use of the institute's far-flung resources. As part of the expansion plans, Reed says, "we spent a lot of time working on culture and communication as things that would help drive the science and interactions among the scientists." That included starting a communications department and making use of the institute's intranet, which is now "a vehicle to communicate with our employees," Reed adds. Videoconference capabilities were beefed up, and a mini "visiting faculty" program was set up to make sure that scientists in Florida spend a few days each year at the La Jolla headquarters, and vice versa. Core facilities played an important role in encouraging collaboration as well. "We've actually purposely set up mutual dependence so that some of those [shared technology labs] are located in California, some are in Florida, and the work gets shipped back and forth," Reed says. "That almost forces, essentially, interaction, dialogue, [and] collaborative work."

Reed credits that collaborative spirit, which has long been a hallmark of the Burnham environment, as a major part of why the institute has been so successful. "We're now the fourth most highly funded research institute in the nation in terms of NIH dollars," he says. While R01 and other single-investigator grants have been cut across the board, NIH and other agencies have been directing more funds to large, multi-investigator studies. Nearly half of the Burnham's funding comes from these mega-scale collaborative grants, Reed says. Scientists from a range of different backgrounds who share a common research interest will pitch in for a grant proposal, "and that becomes a project team for a particular grant," he adds. "It's an ensemble of talents to together approach questions that you just couldn't do if you were working on your own." (Reed, who continues to run his own lab focusing on apoptosis, is on 11 grants at the moment; that large number is because each of the grants is a team-based effort, he says.)

Chemical genomics

While all of the Burnham's research centers on programs that are medically relevant, the institute knows its strengths — and those don't include fully developing drug compounds. "Our budget is significant for an academic center, but nowhere near a pharmaceutical company's," says Thomas Chung, who heads up the institute's chemical genomics program.

The institute has a number of programs that include technologies typically seen in the drug discovery setting — these include high-throughput compound screening, RNAi libraries, structural biology, and more — but Reed says the goal is to get to a "preclinical lead" and then hand it off to a pharmaceutical partner or spin it off to a new company. The Burnham team performs exploratory tox studies, but stops short of the kind of toxicity testing required by FDA or the heavy-duty formulation work necessary to turn a compound into a marketable drug.

The chemical genomics program is part of NIH's Molecular Library Screening Center Network and, as part of that, it has a mandate to "deliver novel chemical probes," says Chung, who has a background in pharma and biotech companies. The center relies on screening tools, assay development, informatics, and functional proteomics to churn out these new chemical entities. Current platforms allow for screening 400,000 compounds per day, Reed says, and a new ultra-high-throughput platform planned for the Orlando facility will be able to handle 2 million compounds daily. Chung adds that the center has invested in a microfluidics-based technology for chemical synthesis, which speeds up solution-based chemistry processes by as much as 10-fold. While "we're not trying to compete with pharma," Chung says, "it's pretty amazing how much pressure we put on ourselves."

The idea of handing off compounds for further validation and development work has paid off for Burnham, which now claims partial credit for four drugs that have been approved by FDA for treatment of cancer, Alzheimer's, and cardiovascular disease, as well as a number of other drugs that are in various stages of clinical trials.

Fast Facts

Burnham Institute for Medical Research
La Jolla, Calif.
President: John Reed

Began: Launched in 1976, the Burnham was originally called the La Jolla Cancer Research Foundation. It officially became the Burnham in 1996.

Staff: More than 800 people, including 85 faculty members

Funding: The institute's operating budget is approximately $113 million. Of that, roughly 80 percent comes from NIH and other sources of federal funding.

Research themes: Formerly a cancer-specific institute, Burnham has expanded to cover a range of diseases. It has five research centers focusing on: cancer; neuroscience, aging, and stem cells; infectious and inflammatory disease; diabetes and obesity; and children's health.

Core facilities: Burnham's shared resources run the gamut from cell imaging to informatics, and include DNA analysis, microarrays, NMR and X-ray crystallography, high-content screening, metabolomics, and more.

Expansion plans: Last year, Burnham opened a center in Orlando, Fla., where it expects to ramp up to 300 staff members within the next decade. The institute's diabetes and obesity center is based at this branch, and technologies used there include functional genomics, chemistry, and pharmacology.

Clinical impact: Burnham research has led to four FDA-approved drugs, and several others are in various phases of clinical trials.

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