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Science & Technology

December 4, 2006
Volume 84, Number 49
pp. 64-67

Scripps Takes A New Approach

Florida campus brings drug discovery to the academic arena

Celia Henry Arnaud

Scripps Florida has no intention of being a clone or, for that matter, of being "Scripps Lite." Instead, Scripps Florida, the new campus in Jupiter, Fla., of the Scripps Research Institute in La Jolla, Calif., is blazing new trails in translational medicine, the branch of medical research in which basic research is translated into clinical practice, especially new therapies.

"Rather than just cloning Scripps Research Institute as it exists in La Jolla, we felt this would be a really good chance to create a completely new model for translational medicine," says Steve Kay, the head of the Scripps Florida steering committee in La Jolla. The old style of translational medicine, in which Ph.D. scientists are "sprinkled" among clinical researchers, has been a "failed experiment," he says.

Scripps Research Institute
Permanent Quarters Scripps Florida's buildings are slated to open in 2009.

A relatively small but key part of Scripps Florida is the Translational Research Institute, which focuses on drug discovery and technology development. The Translational Research Institute has much the same structure as a drug discovery company, and many of the researchers have pharmaceutical experience.

"We got the drug discovery piece going early because it takes time for that to be productive," Kay says. "We got the technology piece up and running early because that was going to be the hook for hiring academic faculty into a small number of departments that center around basic research but with a biomedical focus."

These departments are yet another way to differentiate the Florida and California campuses. "We want to build academic programs in areas that would be complementary to what we have in La Jolla without replicating them," Kay says. To that end, Scripps Florida includes a department of cancer biology and the oddly named department of infectology. The Florida outpost also plans to add a department of regenerative medicine.

Even before its permanent facilities are complete, Scripps Florida is drawing big names from a number of fields. For example, William R. Roush, previously the chairman of the chemistry department at the University of Michigan, Ann Arbor, came aboard to lead a drug discovery effort. Charles Weissmann, a world-renowned molecular biologist and expert in prions, heads up the department of infectology. John Cleveland, a biochemist formerly of St. Jude Children's Hospital in Memphis, joined the faculty just last month as chairman of the cancer biology department.

Patrick Griffin oversees the drug discovery operation. Prior to joining Scripps, he worked at Merck and at ExSAR, a drug discovery company in Princeton, N.J. For the drug discovery projects, "we have to look at building to our strengths," he says. Scripps Florida has established a high-throughput-screening system that would be the envy of small biotech companies and other research institutes but is commonplace in big pharma, Griffin says. Because an operation the size of Scripps Florida can't compete with the Mercks and Pfizers of the world, it needs to "be clever in how we screen the targets," Griffin says.

Scripps has put lots of power into its high-throughput-screening facility. The centerpiece of the facility is a Kalypsis robotic arm, which is based on the type of robotic arm used in automobile manufacturing. Peter S. Hodder, who helped set up a facility at Merck that uses the same kind of robotic arms, oversees the facility and Scripps's efforts to build a compound library. Louis Scampavia manages the day-to-day operations.

Scripps Research Institute
Industrial Scale A heavy-duty robot performs screening campaigns in the drug discovery program.

Scripps Florida selected the robotic arm for its robustness and limited maintenance requirements. "This arm is in many ways overkill. It's like getting a Hummer to take the kids to school," Scampavia says. "It needs almost no maintenance, except maybe a few rings and lubrication annually. An arm like this could last a couple of decades easily. With proper maintenance, it could probably last a century."

The facility has been up and running for a year. Within the first couple of months, they had already run 20 major screening campaigns, Scampavia says. They run a variety of enzymatic, biochemical, and even cell-based assays.

The high-throughput center is part of the Molecular Libraries Screening Centers Network established by the National Institutes of Health as part of its Roadmap Initiative, which identifies major opportunities and gaps in biomedical research. "One of the reasons we're working with NIH and other academicians to provide access to this technology is because it's unavailable to most academic groups in the U.S.," Scampavia says.

Philip LoGrasso, the head of discovery biology at Scripps Florida, was drawn by the opportunity to do drug discovery research in an academic setting. He had previously worked at Merck and at a small biotech start-up.

"What was attractive about Scripps was that it wasn't big pharma, so you don't have the rigidity of big pharma, and you don't have the uncertainty of a venture-backed biotech operation," LoGrasso says. Another attraction was the "trifecta" of drug discovery, advanced technology, and basic research. "If we do something clever and neat in the basic research realm, then we can plug it into drug discovery," he adds.

The drug discovery group has all the components of drug discovery and many of development, including molecular biology, biochemistry, cell biology, pharmacology, medicinal chemistry, high-throughput screening, and drug metabolism and pharmacokinetics.

Scripps chooses its projects carefully. "We don't want to compete with Merck or Pfizer or Glaxo, because we'd probably lose. They can put 40 chemists on a project, and we can't," LoGrasso says. "What we can do, strategically and scientifically, is pick targets that pharmaceutical companies aren't interested in."

For example, Scripps's drug discovery group has a project in Parkinson's disease. "Most pharmaceutical companies have stayed away from Parkinson's because it's a $400 million or so market," LoGrasso says. "We felt if you take the first five years of risk away and present somebody with a nice [investigational new drug] molecule, then a $400 million or $500 million market becomes attractive."

Scripps is looking at several therapeutic areas in addition to Parkinson's, including cardiovascular disease and type 2 diabetes. What's more, Scripps has identified a single target with multiple therapeutic applications, including angina, erectile dysfunction, and spinal cord injury. "We picked that target because you get more shots on goal therapeutically," Lograsso says. "If it works, you really have a lot of potential."

Roush was excited by the opportunity to be involved at Scripps Florida from its early days. In addition to leading a traditional academic research group in organic chemistry, Roush is the executive director of medicinal chemistry in the drug discovery program. "What's new about Scripps Florida is the translational research institute," Roush says. "We've built an academic unit that's focused on drug discovery, but we're doing this in a way that's very different from the way an academic research program would be pursued."

Roush is uncomfortable when people characterize the drug discovery program as a biotech company within the walls of the institute. "We have intentionally brought in a considerable number of people who have substantial drug discovery experience and expertise," he says, "but we're not a biotech company."

Neither is it your typical "mom-and-pop" academic drug discovery program, Roush says. "We've built the infrastructure where we have all the technologies and resources in place to do what is necessary to get insight into the problems at hand."

For example, the Parkinson's program requires compounds that can get into the brain. "I don't know how many academic scientists actually do brain penetration studies," Roush says. "Well, we do them here. We get the data we need so that we can make the appropriate assessments of where we are."

He and his colleagues make those assessments on an ongoing basis, Roush says. They decide whether to continue projects or pull the plug in weekly team meetings, project meetings, and management meetings. "I've been involved in a number of collaborative academic research programs," Roush says. "None of those ever had anything close to this amount of rational decision-making."

The business plan for Scripps Florida requires that the drug discovery program help pay for operating the facility through royalty payments. The drug discovery group also has outside collaborations that bring in research funds. For example, Poniard Pharmaceuticals (previously known as NeoRx), South San Francisco, is funding research on protein kinase inhibitors. Scripps retains the intellectual property, and Poniard has the opportunity to license the compounds. "It's a win-win situation," says Chris Liang, director of medicinal chemistry at Scripps Florida.

All of these advances have been happening as Scripps Florida has been weathering uncertainties in its final location and even its very survival.

Scripps initially agreed to establish a second campus in Florida after the state and Palm Beach County offered funding totaling nearly $500 million. Originally, Scripps Florida was going to be located at a site called Mecca Farms in an undeveloped region of Palm Beach County. But environmental and real-estate issues threatened the project, and at the beginning of this year, it looked like Scripps Florida might die before it was born.

A change in location resolved these issues. Scripps Florida's permanent buildings will be built on the campus of Florida Atlantic University, literally 50 yards from Scripps Florida's temporary location.

Scripps Florida's staff now is shoehorned into temporary buildings on the university's campus. The second temporary building, 33,000 sq ft, just opened in September, with the official ribbon-cutting in October.

Before the second building was ready, the researchers were crammed into a single 41,000-sq-ft building. Some people found themselves sharing an office with as many as five other scientists. The new building has relieved some of that pressure, but some people are still in tight quarters. Assistant professors and scientific staff are still sharing offices. Nearly 200 people are on the ground in Florida, and that number continues to grow as Scripps recruits faculty members.

The tight squeeze has been intentional, management says, to allow the campus to ramp up its scientific programs quickly. "You can't be carrying some massive overhead," Kay says.

Harry Orf, vice president for scientific operations at Scripps Florida, suspects that space constraints will continue until the permanent facilities open in 2009. "While there has been a little bit of decompression," he says, "by the time the permanent facility is ready to take us, we will be just as crowded as we are now."

It's now just a matter of riding out the construction period. The three permanent buildings will have space for a staff of 1,100. Richard Lerner, president of Scripps Research Institute, estimates that staffing at Scripps Florida will top out at between 600 and 1,000 people, depending on government funding and private philanthropy. For the first several years after the permanent buildings open, Kay estimates, Scripps Florida will hire at least 10 new faculty members annually.

Scripps Florida is positioned to take advantage of large federal grants that focus on collaborative interdisciplinary research, Kay says. "We've tried to position Scripps Florida to align with the priorities that NIH seems to be rolling out," he says.

Furthermore, Scripps is determined that although its two campuses are separated by thousands of miles, they will indeed be a single institute. Communication is the key to making sure such unity is the reality. A regular scientific exchange, in which scientists from one location give presentations at the other, is helping establish connections between researchers, and collaborations are already under way.

Scripps Florida is still "very much a work in progress," Roush says. "The good news is that nothing is so irreversibly written in stone that it can't be changed. It's an experiment, and we're all experimentalists at heart. If we put a system in place that doesn't work, we will change. We'll evolve and do what is necessary to build an organization that is wildly successful."

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