Skip to main content

Neurotoxin Discovery Earns 2021 AAAS Newcomb Cleveland Prize

The American Association for the Advancement of Science (AAAS) Newcomb Cleveland Prize, the organization’s oldest award, recognizes an outstanding original research paper published in Science each year. This prize is generously supported by The Fodor Family Trust.

The winning paper is chosen based on the quality of its scholarship, innovation, presentation, likelihood of influencing its field, and its wider interdisciplinary significance.

This year, AAAS is presenting the prize to the paper entitled “Hunting the eagle killer: A cyanobacterial neurotoxin causes vacuolar myelinopathy,” first published March 26th, 2021.

The paper was the product of an international collaboration co-led by Susan Wilde, associate professor of aquatic science at the University of Georgia and Timo Niedermeyer, professor of pharmacognosy at Martin Luther University Halle-Wittenberg in Germany.

At Degray Lake, Arkansas in fall 1994, a mass die-off of bald eagles initiated a wildlife investigation. Dozens of birds died and many displayed odd behavior like missing their perches and flying into rock walls.

When wildlife biologists examined dead eagles, they found extensive lesions throughout their brains and spinal cords. By 1998, scientists knew that birds from at least 10 different southeastern reservoirs in 5 states had this new disease, called vacuolar myelinopathy or VM. But no one knew the cause.

In an email interview with AAAS, Niedermeyer explained how he first became interested in studying these issues. “When I was 12 years old, I was on holiday with my parents, and we visited a show with birds of prey in a medieval castle, where the falconer showed us how the people back then hunted with falcons etc. After the show, we kids were invited to come forward and take a bird on our arm. I chose a bald eagle, and I remember the weight of the bird, me looking at it and the bird looking at me – I was really impressed by this animal, and the bald eagle was one of my favorite animals since,” he said. “Some 25 years later I started working with natural products from cyanobacteria, and by chance, a blog post came up discussing that maybe a novel cyanotoxin might be responsible for bald eagle deaths. I was intrigued by this story, as it combined one of my favorite animals and my new love for cyanobacterial metabolites, so I read a bit about this and came across a press release from UGA, citing Susan. I wrote her an email, asking if she already knew the structure of this toxin. She answered that she did not yet know, and I offered my support, which she accepted. That’s how the journey started.”

In an email interview with AAAS, Wilde noted the pivotal role eagles play in the ecosystem. “Eagles are at the top of our aquatic food chains and a valuable indicator of the environmental health,” she noted.

Wilde and her UGA colleagues documented that VM impacted more than just avian species – they also found that it affected amphibians, reptiles, and fish.

Researchers made gradual progress uncovering the cause. Wilde and her colleagues in South Carolina where many birds suffered from VM. They found dense growth of the invasive plant Hydrilla verticillate. The plant, imported from India for use in aquariums, was overrunning manmade lakes in the southeast, readily consumed by coots, which are frequently eaten by bald eagles.

Using fluorescence microscopy, Wilde observed that in affected waterbodies, Hydrilla leaves were densely covered with cyanobacteria colonies. This novel cyanobacterium was also found in the reservoirs where birds had died. Wilde and her colleagues speculated that the cyanobacterium produced a toxin responsible for the eagle deaths. They fed plants collected from affected waterbodies to laboratory birds, confirming the plants colonized by cyanobacteria caused VM. The cyanobacterium was named Aekthonos hydrillicola – Greek for “eagle killer living on Hydrilla.” However, no known toxin was detected in the cyanobacterium.

Back in Germany, Niedermeyer and co-authors grew this cyanobacterium in the lab. However, lab-cultured bacteria did not cause VM in test chickens. Hypothesizing that the toxin might be produced in lakes but not in the lab, they collected more Hydrilla leaves from impacted lakes. Direct analysis of the cyanobacteria growing on these leaves revealed a compound not present in the lab-grown Aetokthonos, that contained five bromine atoms.

The team was able to reproduce the compound in the lab when the cyanobacteria were grown in the presence of bromide. The compound was revealed to be a novel biindole-alkaloid and further experiments confirmed it causes VM. The scientists called the compound “Aetokthonotoxin” – “toxin that kills the eagle.”

Jan Mares at the Biology Centre of the Czech Academy of Sciences led the genome sequencing of Aetokthonos hydrillicola, which allowed the identification of the compound’s biosynthetic gene cluster. Bromide can leach from rocks, but it can also be introduced into the environment from human activities, such as coal-fueled power plants or water treatment facilities. The authors recommend increasing monitoring and public awareness campaigns be implemented for Hydrilla and aetokthonotoxin to protect both wildlife and human health.

The study brought researchers together from multiple countries and disciplines to solve a decades-old mystery, and it reminds us how dangerous human-induced changes to ecosystems can be. These unanticipated effects are only likely to increase as we continue to alter the world around us.

Niedermeyer offered two key takeaways from the research. “I think we have two aspects here,” he told AAAS. “One is the direct action that can now be taken. We can increase monitoring and awareness for the toxin-producing cyanobacterium and the plant it grows on, Hydrilla. We can avoid introducing bromide into the environment – it might come from… coal-firing power plants, waste incinerators, fuel additives, flame retardant and other chemical industry, biocides used in pool, cooling or industrial water treatment, the gas- and oil-drilling industry, etc.”

He also suggested there is a more general takeaway. “The other aspect is more general; our research shows that human actions can have unanticipated effects,” he said. “Humans have brought a plant from its natural environment in Asia to the US, where it was released and now is invasively spreading. This invasive plant can host a cyanobacterium (we do not yet know where this came from), and the plant also can enrich bromide from the lake water – which the cyanobacterium needs to produce the toxin. Most likely, the bromide comes from human activities (but this would need confirmation in subsequent studies).”

Wilde agreed. “We need to better inform the public and get more eyes on this novel risk to aquatic environments that sustain us all,” she said. 

[Associated image: Jim Ozier]