Algal Blooms: Toxic, But with Possible Drug Potential
April 24, 2020
In 2016, a massive algal bloom surfaced on ocean waters from Maine to Long Island. This splotch on the water shuttered shellfisheries Narragansett Bay-wide in Rhode Island and prompted a recall of about 5 tons of shellfish in Maine. But even before this event, algal blooms have poisoned shellfish, people, and seabirds throughout history, and Matthew Bertin, an assistant professor in the Department of Biomedical and Pharmaceutical Sciences at the University of Rhode Island, wanted to know why.
“When I go out in Narragansett Bay, I’m usually down at Rome Point looking for seals or maybe fishing,” Bertin said April 14 during a webinar hosted by Rhode Island Sea Grant. “But now we really want to focus on what we can’t see in the water. We want to focus on microscopic organisms like algal cells.”
As algal blooms have become more common, possibly owing to warming waters caused by the climate crisis, so have instances of shellfisheries being closed because of potential contamination.
“An increase in bloom events and toxin production represents a significant risk to the state’s shellfish industry,” Bertin said.
He went on to note that it really is a double-edged sword when it comes to harmful algae blooms (HABs).
“I really have two stories to tell. The first story is going to be about HABs and toxin monitoring that we’re doing in Narragansett Bay, and then I have a second story where we are going to use some of the toxin monitoring tools to investigate HABs for new potential drugs,” Bertin said.
Algae, including the toxin-producing Pseudo-nitzschia and cyanobacteria (blue-green algae), are everywhere in the ocean, but normally you can’t see them unless they begin to rapidly increase in number, causing a so-called algal bloom.
“These blooms cause harm in several ways. One is that they can deplete oxygen in water because they’re so high in cell number; the second is physical contact with other aquatic or marine organisms. They can actually attach to and clog fish gills,” he said. “But the biggest harmful aspects of these algal bloom are the production of toxins.”
Humans are exposed to these toxins either from swimming in contaminated water or from eating contaminated shellfish.
“Shellfish that we enjoy consuming can accumulate the toxin domoic acid by direct filtration of plankton in the water,” Bertin said. “As these shellfish are filter feeding, they are trapping cells in their gut, and those cells could contain that toxin.”
He noted an event in 1988, when four people died after eating shellfish from Prince Edward Island in Canada. The culprit was the algae Pseudo-nitzschia and domoic acid, which can cause short-term memory loss, brain damage, and death. This was the same algae that made up the massive bloom in 2016.
Pseudo-nitzschia isn’t new to Rhode Island. It’s been in Narragansett Bay for more than 50 years, according to Bertin.
“However, the first emergency shellfish closure in Rhode Island due to domoic acid being in the shellfish, that didn’t occur until October 2016,” he said. “And then again in March 2017, so these closures are happening here, and they’re happening with cell numbers that are much lower than what has been seen historically. So we’ve been trying to understand what’s driving these new toxic events.”
This work has involved taking samples from Narragansett Bay every week for more than two years. The results of this initiative, while still ongoing, point toward two interesting ideas: toxin production is likely due to a limitation in one or more of the key nutrients required for growth in phytoplankton; and that Pseudo-nitzschia composition is different from season to season.
“But we’re not trying to infer too much in the data at this point. We’re just trying to identify patterns that we can explore further,” Bertin said.
While the negative consequences of these algal blooms and their increased frequency are apparent, Bertin and his team of researchers have found evidence of a potential silver lining.
It all started decades ago with hungry sea hares.
“One of the most interesting discoveries in the history of drug discovery, not just from cyanobacteria, but really from anywhere, is the story of a molecule called dolastatin,” Bertin said. “It was originally discovered decades ago, when natural-products chemists were going out all the time and collecting everything they could find in the ocean, and one thing they were looking at was an organism called a sea hare.”
Sea hares are large, colorful sea slugs that, if domesticated, thrive on a diet of parboiled lettuce and dried kelp. In the wild, they also consume cyanobacteria.
“In these sea hares, these researchers found dolestat, a very, very toxic peptide molecule, and they tried to make it into a drug for a long time,” Bertin said. “Years later, someone found that same dolestat molecule in one of these cyanobacteria. So it turned out the sea hare was eating the cyanobacteria, and was concentrating it in its body to ward off predators.”
This molecule found in the gut of sea hares was eventually turned into an antibody-drug conjugate called Adcetris that’s used to fight cancer.
With this in mind, Bertin and his team are trying to develop other drug leads from cyanobacteria blooms.
“We think there’s a lot here in the realm of drug discovery with these blooms,” he said.