Across North Carolina, regions find their biotechnology niches: aquaculture in the Southeast, medical technology in the East, tissue regeneration, nanotechnology, other specialties elsewhere.

Raleigh-Durham, home to Research Triangle Park, major universities and more than 300 bioscience companies, ranks alongside Boston, San Diego and San Francisco as the nation's top biotechnology cities. But from the mountains to the coast, other regions in North Carolina are busily carving out niches of their own. "Few states are so well able to incorporate biotechnology widely across their landscape as North Carolina," says Steven Burke, senior vice president of corporate affairs for the North Carolina Biotechnology Center in Research Triangle Park.

Helping all regions of the state develop--and gain from--biotechnology is a strategic thrust of the center, a nonprofit established in 1984 to support biotechnology research, business and education statewide. To accelerate regional development, it has opened regional offices in Winston-Salem, Asheville, Greenville and Wilmington. One will open this year in Charlotte. "All of these regions can be strengthened over time by targeted assistance, identification of niche areas, increased partnerships and focused leadership," Burke says.

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A tour of the state reveals a diversity of biotechnology research and product development under way. Southeastern North Carolina is known for its beaches and the entertainment they provide. But the Atlantic Ocean, the brackish wetlands, moderate climate and nearby inlands also present a unique opportunity for scientists interested in researching aquatic life and agriculture. A growing number of researchers from UNC Wilmington, colleagues associated with UNC Chapel Hill and marine scientists from Duke University are exploring ways to detect and treat diseases. "We're seeing a renaissance in marine biotechnology that's introducing us to a whole new set of untapped natural resources and commercial opportunities," says Randall Johnson, director of the Biotechnology Center's Southeastern Office. "It's becoming obvious that this unfolding vein of potential is beginning to contribute mightily to the state's economic and social well-being."

He cites the work of Dr. Daniel Baden, director of the UNCW Center for Marine Science. Baden and colleagues have found ways to turn more than 25 marine toxins into tests and treatments for human health. Their progress has yielded Ocean Solutions, a fledgling company. "If you understand how a molecule works, even in a toxin, you can sometimes devise ways to use it for therapeutic purposes," Baden says. "Take Botox, or botulinum toxin. It's one of the most lethal toxins known, yet by examining its workings doctors were able to develop it as a cosmetic tool."

Perhaps the most exciting avenue being explored is a therapy for cystic fibrosis. The potential treatment is extracted from organisms that cause red tide, algal toxins that can be deadly to fish, turtles, sea mammals and humans.

But Baden and colleagues, working with Wilmington-based aaiPharma, are preparing to seek a development partner to take their discovery through clinical trials and into the marketplace. "It's classic molecular modeling," he says. "In this molecule, we found that it caused an increase in the rate and efficiency of mucus clearance. From there, we simply asked what kind of human conditions involve mucus that doesn't clear effectively." The researchers first targeted cystic fibrosis but may also look at chronic pulmonary disease and smoking.

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MARBIONC, an acronym for Marine Biotechnology in North Carolina, is a program established two years ago by the General Assembly. Scientists are probing new possibilities for improving food fish, aquarium fish, coral and oyster reproduction, as well as new targets in human health. "We're talking about biotechnology markets that could include everything from the food and beverage and technology industries to life sciences and public health," Baden says.

Biotechnology Center grants have spurred research. A faculty recruiting grant enabled UNC-W to recruit Jeffrey Wright, whom Baden calls "an instrumental faculty member." Other grants have funded a fluorescent microscope enabling organism identification for harmful algal bloom species, a high-resolution mass spectrometer for chemical analyses and a DNA sequencer. "The North Carolina Biotechnology Center has been a big part of the reason that biotechnology here has become as good as it has," Baden says.

Developments in the East have taken a different path. Anton-Lewis Usala came to Greenville in June 1990 to have access to a raw material that would allow his company, based in Cleveland, to expand testing of beta cell transplants for diabetes in hopes of eliminating the need for insulin shots. He not only found the raw material, pig pancreas, in large supply, but also a new home for his company, Encelle, which aims to repair diseased or damaged tissue. During the process, Usala accepted a position with East Carolina University's Brody School of Medicine. Usala is working on two new ventures: CTMG, which seeks to accelerate the clinical-testing phase of drug approval, and Ectocelle, a tissue-regeneration company. His work is just one of several research activities developed in the region, says John Chaffee, director of the Biotechnology Center's Eastern Office in Greenville.

"Right now, the strength of this region is in the biomedical device field and in cardiovascular disease research," Chaffee says. "However, significant research activity is emerging in several other biotechnology-related areas such as plant-derived medicinals and the study of metabolic disorders."

ECU has long been a worldwide leader in minimally invasive robotic heart surgery. Doctors now commonly perform robotically assisted mitral-valve repairs. In 2008, ECU will expand its heart treatment and research work with the opening of the $210 million East Carolina Cardiovascular Research Institute, a collaboration between Pitt County Memorial Hospital, University Health Systems of Eastern Carolina and the Brody School of Medicine. The institute should generate more than 500 jobs and add $34 million yearly to the economy. "The combination of the university-based research and the companies present will pay great dividends for the future of the region," Chaffee says.

The Eastern Region's work in bioscience isn't focused solely on medicine and medical devices. Beaufort County will soon be the home of a $150 million ethanol plant that will produce 114 million gallons of ethanol per year from biomass. The plant, to be built by Agri-Ethanol Products, will be the first on the East Coast. It will consume more than 20 million bushels of grain per year.

In the Piedmond Triad region, new medical therapies are not only moving from the lab to the clinic but are making history as well. While at Harvard University, Dr. Anthony Atala used a human tissue sample to create a bladder--the first human organ developed using tissue engineering. Atala's work, focusing on growing human tissues and organs to repair those defective at birth or destroyed by disease, has led to the construction of blood vessels, wombs and heart valves. Thanks to a multimillion-dollar recruiting effort by Wake Forest University, coupled with plans to build an Institute for Regenerative Medicine, Atala is continuing his work in North Carolina at the Piedmont Triad Research Park in Winston-Salem.

As a result of Atala's move, Tengion, a company created in part to use the professor's research, has opened a Winston-Salem office and could have 160 employees by 2009. "It's a great opportunity to be in an area with an emerging park," Atala says. "Having the academic environment and the research park is a powerful combination."

Atala's work highlights the Piedmont Triad's change from an area steeped in tobacco and furniture manufacturing to one embracing technological advances. For example, Targacept is developing treatments for central nervous system diseases by targeting nicotine receptors in the brain. The work stems from years of research by its parent company, R.J. Reynolds Tobacco.

In High Point, TransTech Pharma is developing technology to identify and test potential drugs faster and more efficiently. TTP Translational Technology includes advanced robotics.

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Also at Wake Forest, the School of Medicine has earmarked a $7.5 million grant from the National Center for Complementary and Alternative Medicine and the Office of Dietary Supplements to study dietary supplements. And the Wake Forest and Harvard Center for Botanical Lipids is studying how flaxseed, echium and borage could treat and prevent atherosclerosis, asthma and other anti-inflammatory diseases. "We are building a base of terrific intellectual property that will eventually find itself in the marketplace," says Gwyn Riddick, director of the Biotechnology Center's Piedmont Triad Office.

In the Charlotte region, nanotechnology--the manipulation of matter on an ultra-small scale--just might be the next big thing. Researchers including Wade Sisk and Ken Gonsalves of UNC Charlotte and Craig Halberstadt and Qi Lu of Carolinas Medical Center are working to create medical treatments using man-made materials about 1,000 times smaller than the width of a human hair.

Researchers are creating "a kind of Trojan Horse" that can enter a cell and rectify what's wrong, Gonsalves says. He's a professor of polymer materials and organic chemistry. "We're actually correcting the machinery of the cell to make it function the way it should." The application could be useful in treating muscular dystrophy and may play an important role in creating tissues to replace ligaments, tendons, muscle, bone and even neurological tissue.

Another promising area of nanotechnology research is photodynamic therapy for cancer treatment. An ultra-tiny "machine" goes to a tumor cell, enters it and generates energy. "The idea is for a target bullet to go to the cell and create a burst of energy that destroys the cancerous cell but not the healthy cells surrounding it," says Gonsalves, who was recruited to UNC Charlotte in 2000 with the help of a $96,000 grant from the North Carolina Biotechnology Center.

Nanotechnology isn't the only game in Charlotte town and gown. Bioinformatics, the storage, retrieval and analysis of large amounts of biological data, also is a dynamic research area, along with biomedical engineering, says Marjorie Benbow of UNC Charlotte's Office of Technology Transfer.

Since 1996, UNC Charlotte has spun off 26 companies, gotten 53 patents and transferred 79 technologies to industry, with much of that activity in the biosciences. That applied-science tradition should play an important role in the North Carolina Research Campus in Kannapolis. The 350-acre campus, being developed by Dole Food Co. owner David Murdock in partnership with the UNC System, Duke University and the N.C. Community College System, is envisioned as a major center for research, business and education in nutrition, agriculture and biotechnology, addressing health problems such as cancer and obesity.

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UNC Charlotte will support the new campus with expertise in bioinformatics, nutrition and health behavior and education. The same data-mining applications and logarithms used to handle financial transactions in Charlotte's large banking industry are also applicable to biological data, says Dr. Larry Mays, director of the university's new Bioinformatics Center.

Renowned for its exceptional geographic and cultural appeal, Western North Carolina is awakening to an important relationship with the life sciences. The region's biodiversity contributes to its rich history in the medicinal use of natural plants and herbs. The region's potential in natural products, forestry and agriculture are "turning on the lights" in regional research labs, says Cheryl McMurry, director of the Biotech Center's Western Office. Broadaxes and dibbles have given way to new tools such as molecular biology, chemistry, bioinformatics and molecular modeling to provide commercialization and to infuse a new economic vitality, thanks to the region's universities and entrepreneurs. UNC Asheville, Appalachian State University and Western Carolina University have expanded their research departments and are participating in tech transfer efforts. More than 30 scientists presented work at a Biotechnology Center-sponsored "Science in the Mountains" symposium in early April.

N.C. State University experts are also contributing to the science base, through horticultural scientists at the Mountain Horticultural Crops Research and Extension Center in Fletcher, home of the N.C. Specialty Crops Program, a multi-agency, statewide program dedicated to the development of new crops for Tar Heel farmers.

"From Christmas trees to chestnut trees, black cohosh to bloodroot, biotechnology's principles are seeding, protecting and improving western North Carolina industries," says John F.A.V. Cecil, president of Biltmore Farms and chairman of the 24-member Advisory Committee for Biotechnology in Western North Carolina.

Increasingly, he notes, the tools of biotechnology hold the key to cultivation of rare medicinal herbs so those in the wild can repopulate. Improved biofuel production may result from installing genes leading to superior strains of rapeseed that can lower the cost of converting it into a domestically generated petroleum substitute.

Asheville-Buncombe Technical Community College's Enka campus, a 37-acre setting with 20 wet labs and more than 277,000 square feet of office, lab, warehouse and light manufacturing space, is a hub of life-sciences entrepreneurial activity. The Biotechnology Center's Western Office is housed there.

North Carolina Biotechnology Center

15 T.W. Alexander Drive

Research Triangle Park, NC 27709

[phone], www.ncbiotech.org