Cyanobacteria, and their toxins, are incredibly diverse. How can risk be measured? 

When a greenish cloud, surface scum or other suspicious algae appears in a previously clear lake, the message is clear: Stay away. As cyanobacteria blooms become more common in New Hampshire, that precaution has become common practice across the state.

The reason? Cyanobacteria, an ancient single-celled organism that multiplies to excess when nutrients and heat are plentiful, can produce toxins harmful to the skin, liver, nervous system, stomach and more. Effects range from mild illness and rash to, in rare instances, death; therefore, authorities like the New Hampshire Department of Environmental Services and the Centers for Disease Control and Prevention urge would-be swimmers, paddlers and pets to stay away from water that shows signs of a bloom.

The effects of cyanotoxin exposure are widely documented. But not all cyanobacteria are toxic and beneficial cyanobacteria are much more common, filling an important ecological role at the base of the food chain. Yet differentiating the two, and determining when and to what extent the organisms pose a threat to health, is a significant scientific challenge. 

There are thousands of known species of cyanobacteria and at least hundreds of variations of the dangerous chemicals the bacteria can produce, called cyanotoxins. But scientists have yet to characterize many of those specific molecules, according to Anyin Li, associate professor of chemistry at the University of New Hampshire.

That lack of knowledge is a major hurdle in efforts to understand how toxins differ, how they affect us and how they travel through ecosystems, Li said.

“It’s one of the reasons, in fact, that a lot of the information you’ll find about cyanotoxins is very general, and focused on sort of potential risk,” he said in an interview. 

Li and other researchers have focused their work on that knowledge gap, turning to molecular techniques they hope will help create an information-rich library of cyanotoxin profiles. Ultimately, researchers said, they hope the work will contribute to efforts to create evidence-based safety regulations while helping people enjoy the water bodies they love without fear. 

Protein detectives

One technique scientists tend to use more than others to test for the presence of cyanotoxins is a molecule-tagging technique called ELISA (short for enzyme-linked immunosorbent assay). The tags tell scientists whether the toxins are present, but the technique has some limitations, Li said. It is vulnerable to false positives — such as when the toxin molecule has broken up but the test still reads it as present — and does not provide the level of detail researchers said would be most useful. 

Within one class of cyanotoxins called microcystins, for example, there are 400 possible subtypes, Li said. ELISA on its own is not enough to differentiate among all of them.

This is emblematic of the challenges associated with other tests scientists have at their disposal to assess cyanotoxins, he added. 

“At this point, many of these tools to look at these toxins, they are too general,” he said. They do not differentiate subtypes, and they do not always allow researchers to estimate the amount of toxin present in a sample. The error rate, he said, is as high as 40%. 

When separate toxin subtypes have the potential to affect the human body very differently, that matters.

In Li’s laboratory, UNH researchers are refining a method of identifying those molecules based on a different molecular technique called mass spectrometry. This technique allows researchers to take minute measurements of the matter in a molecule, yielding information so precise they can be analyzed to identify specific toxin subtypes. 

So far, the technique has allowed Li’s lab to identify those subtypes with more precision than other methods. 

Cyanobacteria genes

Another way to learn more about what a bloom may be producing is to get specific about the types of organisms it contains, said molecular biologist and algae expert Robin Sleith and microbial ecologist Pete Countway, both researchers at Bigelow Laboratory for Ocean Sciences in Boothbay, Maine. 

Because cyanobacteria are single-celled and incredibly diverse, defining species boundaries between them is difficult, Countway said. 

Regarding single-celled organisms in general, “that’s something we’ve been struggling with, you know, for my entire professional career,” he said. 

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Instead, he said, it helps to consider the organisms’ entire genetic sequences. Determining whether the organism may pose a risk to human health, then, requires the scientists to work forward along the path from DNA to protein building blocks to finished toxins. Decoding genes is the first step.

Sleith and Countway analyze DNA collected from the environment, also known as eDNA, and DNA from cyanobacteria samples, as well as other potentially harmful microorganisms, looking for the genes that could allow the creatures to make toxins. 

Just the presence of a toxin gene doesn’t mean it’s being produced, however, so another test, like ELISA, may follow. 

While this method can help identify harmful toxins when they are present, it can also be a way to alleviate concerns. In a paper published this September in the journal Harmful Algae, Sleith, Countway and their co-authors demonstrated that the toxin-producing genes were not present in one species of cyanobacteria that can appear in lakes. 

Cyano knowledge is power

Learning more about the diversity of cyanotoxins is crucial because, by their nature, cyanobacteria are all around us, said Amanda McQuaid, a professor of water quality and ecotoxicology at UNH and director of the university extension’s Lakes Lay Monitoring Program. 

The tiniest cyanobacteria can be airborne, for instance, making their way into people’s lungs, while others are found nearly anywhere there is water, she said. But in most cases, this is normal and not cause for alarm. 

Yet, there are also circumstances where precautions against health impacts are necessary. Scientists haven’t yet pinpointed exactly what level of toxin exposure is dangerous, but McQuaid said she hopes more precise research would help. 

This is Li’s goal, too: He hopes to see more precise evidence aid the development of federal exposure guidelines.

“Better quantitative methods will allow us to define more specific guidelines,” he said. “Right now the EPA guidelines are very general.”

Making these measurements more widely available is also important, said Sleith and Countway. That would require development of accessible, fast water tests using some of these techniques. 

“Basically, we’d need to see it become as standard as, like, home COVID tests,” Countway said.

More precise testing will also allow scientists like Anna O’Brien, UNH assistant professor of molecular, cellular and biomedical science, to track toxins as they cycle through ecosystems, she said.

As an example, O’Brien pointed to duckweed, a small aquatic plant that absorbs nutrients from pond water as it grows. By adding the plant to soil, farmers could access a readily available source of “green” fertilizer, O’Brien said. But scientists must first ensure that they would not also be plying their croplands with cyanotoxins, something O’Brien hopes a better understanding of the toxins will rule out. 

With climate change contributing to hotter summers and warming water bodies in the Northeast, cyanobacteria blooms are likely to remain prevalent. 

“What I see on the horizon is that these blooms are getting, especially in the Northeast, it’s probably going to get a little bit worse before it gets better,” Sleith said. 

But with the right tools and increased knowledge, he’s hopeful people will be able to navigate the coming years safely.

“What I want is for people to feel safe about enjoying their time in the water,” he said.