Dan Baden, Marine Scientist

By Jim Shamp, Senior Editor

Mention red tide to some folks and you might conjure an image of a romantic ocean-side sunset.

But for millions of Florida beachgoers the occasional algal blooms dubbed red tide are anything but romantic. They can be debilitating – sometimes deadly – for fish, shellfish and other marine creatures such as manatees, and for people – especially those with asthma and other airway diseases.

During a Florida red tide bloom, patches of salt water turn a bloody color from a population explosion of a tiny dinoflagellate, Karenia brevis. And for the past decade, researchers, led by a team from the University of North Carolina Wilmington’s Center for Marine Science (CMS) have joined Florida beachgoers to collect data and samples, seeking to better understand the damage wrought by red tide.

The scientists have discovered that winds blowing across the algae-saturated water pick up microscopic particles of a lung-irritating substance called brevetoxin, released when the algae break open. It’s not a protein, they discovered. Instead, they identified it as a ladder-frame polyether. It can be poisonous to fish, shellfish and carnivores that eat the poisoned food. And a fine mist of aerosolized polyether can float through the air long distances and cause sometimes-severe airway symptoms when inhaled by humans and other air-breathing creatures.

The phenomenon turned into an opportunity, however, for Andrea Bourdelais, Ph.D., associate research professor at CMS. Bourdelais was trained as a pharmacologist/toxicologist, but is now a natural product chemist – an unusual pairing of disciplines that proved to be a perfect blend for some “aha” developments coming from the CMS red tide research. She is part of an eclectic array of scientists and other specialists assembled in the unique 100,000-square-foot research facility by CMS’s director, Daniel Baden, Ph.D.

Visitors who walk past the colorful and soothing displays of live and sculpted marine life in the center’s lobby and peer down the halls into the researchlabs might find a geologist next to a chemist next to a biologist next to an oceanographer next to an engineer. Baden, a biochemist, is committed to this mixing of disciplines, talent and ideas – and to the commercialization opportunities enabled by this kind of mix.

Bourdelais said she believes her dual interest has been a benefit to her search for new compounds.

“I came from a pharmacology background and went into natural products. Normally when a natural products chemist screens extracts from organisms, we’re looking for biological activity – toxicity, activity in a certain bioassay and so forth. As we screen our extracts, the toxins are what get the ‘hits.’  If you’re screening substances that don’t have a ‘hit’ showing biological activity in your test, they’re usually thrown out.”

Bourdelais got really curious, though, when she came across some strange findings while conducting routine toxicity screening on brevetoxin. “We found this peak that went along with toxins, but it wasn’t toxic. Naively, I went down the hall and told Dan. He wasn’t concerned, and said just move on. But I told him I thought this one toxin was having variable activity. I thought maybe it was an antagonist that could block the activity of the toxin. He said, ‘Well that would be new.’”

Baden supported Bourdelais’ curiosity. He let her learn to operate the center’s nuclear magnetic resonance (NMR) and mass spectrometry equipment – tools not commonly used by a pharmacologist.

“Dan was great,” said Bourdelais. “He let me take the time to learn NMR and mass spectroscopy so we could figure out what this was. A lot of people wouldn’t have given me time to do that. But he lets people with a wild hair follow their instincts. And generally it turns up interesting things.”

Her “antagonistic” hunch proved right. Bourdelais has already secured two patents on discoveries stemming from her red tide research, including one aimed at affecting mucus transport in the lung as a potential treatment for diseases like cystic fibrosis. She and her colleagues bring in some $1.5 million a year in federal funding for what Baden laughingly refers to as their “beach to bedside” research – a twist on the more common reference to “bench to bedside” R&D goals.

Some of the CMS study of algae and other tiny samples is also conducted on a high-end microscope purchased by Professor Carmelo Tomas, Ph.D., with Institutional Development Grant funding from the North Carolina Biotechnology Center.

Three years ago Bourdelais won the Jack L. Beal award for the best paper
by a young investigator in the Journal of Natural Products. The paper described her lab’s discovery of the neurotoxin antagonist compound, which she called brevenal.

“The Center for Marine Science is a fantastic resource,” said Randall Johnson, director of the North Carolina Biotechnology Center’s Southeastern Office, also in Wilmington. “Dan Baden and his team are on the front lines of marine scientists delving into a new world of discovery opportunities on and in our oceans. This relatively untapped biological diversity is almost certain to be a key to breakthroughs in medicine, energy and a host of other solutions to human quandaries.”

Bourdelais said years of animal testing and clinical trials lie ahead before any human therapy can come from her research. “Right now we’re just accumulating enough brevenal to do animal and toxicology studies. We need about 40 milligrams, but it’s tricky to come up with – and we’re not the only ones who need it.”  But she’s not daunted.

“For the past couple of years most of what I’m doing is isolating brevetoxins and looking for new ones, hopefully to find new activity,” she said. “I really like to work in the lab. I’m fortunate enough to be able to spend about 75 percent of my time in the lab. Most people aren’t lucky enough to do that.”

Baden is glad to accommodate. He even has plans to expand the growing, already-crowded CMS facility. But like many other capital projects across the state, this one is on hold pending a turnaround in the struggling economy.

Even though things are crowded at CMS, there are some advantages to rubbing elbows.