TRANSLATING ACADEMICS TO APPLICATIONS
Today's basic research transforms tomorrow's medicine and technology.
Stem cells are more or less the body's blank-canvas cells that can produce virtually any others; they promise huge advances in medicine, perhaps one day even curing spinal injuries and more. There are problems, though: where to get the cells and how to do it under federal funding. A new approach to harvesting stem cells was recently deliniated by Anthony Atala and his colleagues at Wake Forest University School of Medicine's Institute for Regenerative Medicine, along with researchers at the Children's Hospital and Harvard Medical School. This team showed that amniotic fluid donated by pregnant woman contains cells that can develop into mature cell types including liver, brain, and bone. In the long term, says Atala, he hopes that patients needing transplants won't have to wait "for someone to die so they can live."
It took Atala's team seven years to prove the authenticity of their stem cells, but the technique could now provide these potentially therapeutic cells for centuries. Other translational research in North Carolina offers similar promise.
An emerging region for translational research around Wake Forest University played a fundamental role in attracting Atala. Three years ago, he moved his team from Harvard University to the urban Piedmont Triad Research Park (PTRP) in downtown Winston-Salem. "There is a concentration of trained research personnel, a high number of opportunities for collaboration, support for tech transfer, and overall, the support of the academic centers, [and] city and state government toward biotechnology," Atala explains. Indeed, the state-funded North Carolina Biotechnology Center helped entice Atala to leave Harvard with a recruitment grant.
The PTRP will serve as incubator for spinoffs from Atala's institute. The lab has produced more than 100 national and international patents. In 2006, Atala and researchers from Children's Hospital of Boston announced that they had reconstructed the defective bladders of seven children with cultivated tissue. A small sample of the patient's own bladder cells were grown on dome-shaped scaffolding, and the new tissue was then implanted in patients to create larger bladders.
The drive to help young patients also inspired Duke University Medical Center's Y.T. Chen to engineer a recombinant enzyme replacement therapy for Pompe disease. Most infants born with Pompe die before their first birthday. In this disease, a defective enzyme allows glycogen to build up in muscle tissue, causing degeneration and enormously enlarged hearts. Chen and his colleagues committed 20 years to development, from genetically engineered cell cultures to Food & Drug Administration approval of Myozyme in April 2006. "Until the approval there was no real treatment for patients with this devastating condition," says Priya Kishnani, a Duke medical geneticist and principal investigator for the clinical trials.
The Myozyme story illustrates the commitment of North Carolina's academic medical centers to developing innovative treatments, Chen says. "We received immense support from the administration." The university's technology-transfer office helped Chen and his colleagues submit a patent request, obtain FDA orphan-drug designation to take the enzyme replacement therapy into clinical trials, partner with a biotechnology firm to manufacture the enzyme, find funding for the trials and further research, and ultimately license the rights for enzyme production to Genzyme in Cambridge, Mass.
Other universities also sponsor large efforts aimed at translational results. At University of North Carolina (UNC) Greensboro, for example, the Center for Biotechnology, Genomics, and Health Research launched the Guilford Genomic Medicine Initiative. The university calls this a demonstration project designed to take genomic medicine into the healthcare system. This project earned $10 million in support from the US Department of Defense, and this initiative includes partnerships with the Duke University Center for Human Genetics and the Moses Cone Health System.
In addition to scientific research, North Carolina medical schools also train faculty as entrepreneurs. For instance, Duke and UNC, Chapel Hill's top-ranked business schools offer classes and programs focused on commercializing inventions. The North Carolina Biotechnology Center also dispenses advice and helps with networking.
In one example of networking's power, UNC, Chapel Hill professor Tom Fischer met entrepreneur Stan Eskridge through a class at the school's Kenan-Flagler business school. Eskridge helped Fischer and cofounder Arthur Bode of East Carolina University form Hemocellular Therapeutics in 2002, now renamed Entegrion. A true bench discovery, Entegrion's original product, dubbed Stasix, descends from a technique to preserve platelets for everyday lab experiments. The freeze-dried platelets weren't suitable for human use, but the concept led Bode and his colleagues to develop a similar lyophilization process for storing and transporting platelets. Surprisingly, the freeze-drying enhanced the platelet's clotting process; after reconstitution in saline solution, the platelets immediately head to wounds and start clotting. Fresh platelets, on the other hand, circulate for about 12 hours after infusion before clotting begins.
Entegrion is one of many North Carolina companies founded by scientists from different universities. Although Fischer and Bode are both pathologists, North Carolina's rich agricultural history also makes it possible for medical researchers to partner with zoologists and botanists.
Donald Thrall, a veterinarian and professor at North Carolina State University in Raleigh, treats spontaneous tumors in pet dogs and cats. Thrall joined forces with Duke radiation oncologist Mark Dewhirst to create new cancer therapies for animals and humans. The pair helped pioneer the use of hyperthermia for targeting chemotherapy, now in clinical trials for breast cancer patients.
The team recently took hyperthermia a step further, thanks to Duke engineer David Needham, who invented coating and encapsulating technology that encases chemotherapeutic agents in temperature-sensitive fatty spheres called liposomes. These scientists also use microwaves to heat a targeted tumor. "Encapsulating drugs in liposomes and infusing them into the bloodstream enables us to deliver 30 times more chemotherapy than we normally could to the tumor site," Dewhirst says. "The liposomes melt only within the tumor, and the rest of the body receives relatively less of the toxic drug." The team has begun testing the liposome-delivered doxorubicin in women whose breast cancers have recurred in their chest walls.
Further south at UNC Charlotte, immunologist Ken Bost and plant biologist Ken Piller partnered to design and develop soy-based edible vaccines for livestock and humans. SoyMeds won a 2006 business competition for UNC-founded companies.
While such novel drug-delivery methods garner significant attention, many North Carolinian researchers also focus on improving the effectiveness of existing treatments through studies of disease genetics and the genetics of human variation. For example, basic research exploring genetic variation in HIV led to a new test identifying which of the drug-resistant strains of HIV are present in a patient's bloodstream. The test proved sensitive enough to detect a single mutated virus out of 10,000 nonmutated viruses in the patients' samples, says Duke molecular virologist, Feng Gao.
Further along are genomic tests to analyze the unique molecular traits of certain tumors and determine the chemotherapy that will be most effective. "Ultimately, our goal is to use these techniques to develop a quantitative tool for selecting each patient's therapy," says UNC, Chapel Hill pharmacologist Howard McLeod, a recent transplant from Washington University in St. Louis. McLeod has expanded his work on tumor variants to assemble a database of gene variants that change the efficacy or toxicity of drugs on the World Health Organization's essential medicines list. "Until now, researchers looking at the role of genetic variation in drug effects have focused mainly on toxic drugs used by specialists treating cancer or HIV infection," McLeod says. "We think it's likely that using pharmacogenetics in the primary-care setting can reduce healthcare costs," he explains.
Discoveries that could reduce healthcare costs can come from surprisingly different fields, including astrophysics. At East Carolina University, physicist Orville Day and mathematician David Pravica hope their mathematical model for detecting black holes will become a device that detects plaque and aneurysms based on vibrations caused by blood moving through arterial walls. The original model predicts the mass and size of black holes from surrounding energy vibrations.
Another physicist, UNC, Chapel Hill professor Otto Zhou, hopes his discovery will lead to small, portable X-ray machines for ambulances, airports, and customs operations. Zhou replaced the metal filaments in standard X-ray machines with carbon nanotubes, which shoot off electrons when exposed to an electric field at room temperature. Metal filaments in most X-ray devices must be heated to 2000°C in a vacuum to release electrons.
On the Chapel Hill campus, chemical engineering wunderkind Joe DeSimone fashioned fluoropolymers that are liquid at room temperature but cure to a transparent solid when exposed to ultraviolet light. "Our method opens the world's door to marrying organic materials to nanotechnology. Biology, after all, is almost exclusively organic materials," explains DeSimone. With his students, DeSimone launched a spinoff company, Liquidia, to mass-produce custom-built organic nanoparticles in any size, shape, or composition.
DeSimone says he encourages an entrepreneurial mindset in his students. "I'm trying to create a culture in my lab for training entrepreneurs," he adds. "The days of companies hiring scientists by the thousands are over. We have to create our own opportunities. Entrepreneurship is becoming a part of the fabric of the university."
Editor's Note (posted 5/31/2007): Subsequent to the publication of this article in print and online, editors at The Scientist became aware that Becky Oskin works in the public affairs office at UNC-Chapel Hill, and was previously in a similar role at Duke. Had this been known to the editors when commissioning this supplement, she would not have been hired to write a piece that involved Duke and UNC-Chapel Hill. However, since the piece has been published, we feel it is necessary to disclose this fact to readers, and we regret the oversight.