Bench to bed: Washington University is carrying research from the lab to practice
This article first appeared in the St. Louis Beacon, Sept. 20, 2011 - When Dr. David Curiel talks about his last institution, the University of Alabama at Birmingham, he marvels at the success of the four decade-old school.
"In 25 years (funding) went from nonexistent to [being in the] top 20 in federal funding," he said. "It's just uncanny."
It's a story he hopes to replicate at the much older educational institution for which he now works. Curiel heads Washington University's Biologic Therapeutics Center, an innovative program launched by the university earlier this year. Run out of an unremarkable four-story office building on Forest Park Parkway, the initiative is designed to emulate the formula that Curiel feels made UAB such a success, a focus on what is known as "bench-to-bed," or translational, research.
"Lots of investigators will do proof of principal in animals. Then they'll publish in a prestigious journal and that's the end product," he said. "That's what Wash U has rewarded you for traditionally, and there may not be the expertise for what comes next."
Curiel, 54, has just the resume to look at what comes next. Sitting in an office with a wall-sized whiteboard, the Atlanta native warms to his subject matter with ease, traversing diverse subjects from regulatory hurdles to research possibilities to the economic realities of modern science with a generally confident sense that they all fit together. A graduate of Emory University's medical school, Curiel earned his Ph.D in the Netherlands. He spent time at the University of North Carolina before going to Alabama where he went on to head that school's gene therapy program. Now, he plays a dual role at Wash U as both the director of the BTC and the Division of Cancer Biology.
The center's mission is not the raw data itself but drugs, antibodies, cells or other agents that become the basis for real-world treatments. Such end products face a dizzying array of challenges, including a flurry of paperwork, stacks of documentation and a lengthy approval process by regulatory bodies. All of it is based on research that must be carried out under highly stringent specifications known as good manufacturer practices (GMPs).
"That's often the narrow neck in the bottle," he said. "You have the most brilliant science and the sickest patients [in need] and unless you can make your agent in GMP quality, you can't get through regulatory and FDA (Food and Drug Administration) trials."
Those practices are embodied in what the BTC staff refer to as "the core," a special 2,600-square foot, high-tech "clean room" about two blocks from Curiel's office, where investigational research can be carried out. Run in conjunction with the Siteman Cancer Center, the specially pressurized facility features six independent research suites, an exacting environmental control program and a somewhat daunting protective gowning procedure for a reporter taking a tour of the antiseptic interior.
The core is a preexisting facility but has been folded into the center. Curiel said it's is a great place to do science.
"At Alabama, we had a unit where we did what was called campaign runs where we'd make an agent. Then we'd have to clean up the whole room," he said. "Then we'd do it again. Here, we have multiple units under one roof so simultaneously we can produce antibodies, cells -- all for final common pathway."
The lab work is all a part of what Curiel terms the "infrastructure" angle. The other half of the center covers what he calls the "ethos" part of the mission, imparting ideas through a monthly seminar series that brings in high-profile, internationally known investigators. It's an aspect that will showcase the cross-disciplined nature of the center. Speakers are booked well into next year.
"That way there will be the telling of the story over and over again in multiple disease contexts," he said.
Curiel hopes the center may lead not just to better research but also to more programmatic grants for the university and more opportunities to put Wash U on the map in the translational field.
"The trials that you get at our cancer center are trials that you couldn't necessarily get out in the community," he said. "Most of the cancer centers in the community are part of organized treatment groups, national or regional structures. Here, we're plugged directly into the National Cancer Institute. We're doing trials that can only be done at NCI centers."
But it will also benefit the scientific community at large, he said. Curiel noted that there has been an ongoing shift in recent years that has tied large percentages of the profits from major pharmaceutical concerns to the fate of a handful of popular drugs. He said this concentration has led to a focus on those products and emptied the pipeline for new research to some degree.
"Everybody would admit that there isn't the kind of development in-house that there was two decades ago," he said.
This has created a shift towards more development by academic institutions that don't always possess the necessary infrastructure to take on such projects. That's where translational research initiatives like BTC come in.
Curiel said that the model previously has been a bifurcated one in which investigators do initial research and publish in widely available journals where drug companies pick up the work and do the heavy lifting to create the final product and go through the regulatory hoops. He proposes a new paradigm that will allow researchers to attract the consumers of their work at a "further downstream" position, one in which they may hold solid intellectual property claims on approved products.
"It's almost like owning the means of production," he said. "If we can do things once here, then when big pharma does business with us, they're negotiating in a context by which we are holding much more of the value of the product."
It's also a process that he thinks will bring new treatments to market sooner since academic units have a somewhat different developmental route through agencies like the FDA. Phase I clinical trials may take only two or three years rather than decades.
"We can develop something and take it to humans where we are asking simple questions. Is it safe? Is there biological efficacy? Drug companies then have to add, 'Is it better than prevailing therapy if we set up a large trial to compare it to our other drugs?'" Curiel said.
David Baugher is a freelance writer in St. Louis.