The fall of 1952 was a busy time of year in Storm Lake, Iowa. Farmers tended to their crops, as the hot, dry summer poured into October, and children eagerly anticipated Halloween. It was especially busy for State Conservation Officer Frank Starr. He spent October burying bodies. A lot of bodies. By his count, there were 8,253, but he was sure he missed a few. He was a game warden, after all, not an accountant. So while his friends spent their Saturdays watching the Iowa Hawkeyes get destroyed on the football field, Frank was digging a field full of holes.
Storm Lake by Denise Krebs (CC BY-NC-2.0)
Frank wasn’t your run-of-the-mill serial killer, though, his job was to collect and dispose of the bodies. The killer was Storm Lake itself. The unseasonably warm fall provided a perfect breeding ground for Ananaena flos-aquae, a filamentous cyanobacteria. The shores and bays of the lake were filled to a “porridge-like consistency” with cyanobacteria colonies, which while not technically algae, are often referred to as such. Early October brought 2,000 dead Franklin’s Gulls and October 29th saw the death of 5,000 more. (1)
By Frank’s account he buried:
Franklin’s Gull by Andy Reago (CC BY-2.0)
- 7,000 Franklin’s gulls
- 560 Ducks
- 400 Coots
- 200 Pheasants
- 50 Squirrels
- 18 Muskrats
- 15 Dogs
- 4 Cats
- 2 Hogs
- 2 Hawks
- 1 Skunk
- 1 Mink
That many dead animals attracts attention and soon the Veterinary Clinic at Iowa State College became involved. They confirmed that, yes, these animals were in fact dead. Moreover, they concluded that they were poisoned “due to a toxic substance incidental to the high concentration of algae present in the water.” This is CSI: Iowa 1952, so I’ll cut them some slack. When they force-fed algae materials to chickens, guinea pigs, and rabbits, they all quickly died. Filtered material injected into mice killed them within minutes, leading to the name Very Fast Death Factor (VFDF), a name I can get behind.
Fast forward a decade to 1966, Canadian researches isolated the responsible toxin and deduced its chemical structure. In 1977 X-ray crystallographic data confirmed the proposed structure and it was given the name anatoxin, I suppose as an homage to the genus Ananaena. Anatoxin is a bicyclic alkaloid that is a selective nicotinic acetylcholine receptor agonist. It is not only selective for the nicotinic receptor over the muscarinic but has greater activity on nicotinic receptors at neuromuscular junctions versus in the central nervous system (CNS). The nicotinic receptors are a subset of cholinergic receptors that are activated by the neurotransmitter acetylcholine and other drugs, such as nicotine, from where it gets its name.
Nicotinic receptors are found throughout the peripheral nervous system where it is used to transmit signals from presynaptic to postsynaptic cells and in skeletal muscle where it signals muscle contraction. At neuromuscular junctions, acetylcholine binds to nicotinic receptors and causes a conformational change, opening a channel that allows for sodium and calcium ions to move into the neuron. This results in an action potential that stimulates muscle contraction. To keep our muscles from permanent contraction, acetylcholine dissociates from the receptor and the enzyme acetylcholinesterase cleaves it into acetate and choline, as a way to keep it from immediately binding the receptor again. (2)
Anatoxin
How does all this relate to anatoxin? Anatoxin has a much greater binding affinity for nicotinic receptors than acetylcholine, about 20 times greater, and binds irreversibly. Once bound it does not release from the receptor, and it is not a substrate for acetylcholinesterase – meaning the enzyme can’t chew it apart. The end result is an ion channel that is locked open and paralyzed. When muscles that we don’t even consciously control in our diaphragm seize up, we stop breathing and die. That’s how anatoxin kills, respiratory arrest, and it can happen within minutes. Very Fast Death Factor, indeed.
Anatoxin is potent and can quickly kill anything that it comes in contact with. Most often this is wildlife and livestock that live in, or drink from, bodies of water contaminated with cyanobacterial blooms like we saw in Storm Lake, Iowa. So what about people? Most people don’t swim in algae-filled ponds and lakes – it’s kinda gross – but there has been one reported death, a 17-year-old boy in Wisconsin. He accidentally swallowed water while playing in a scum-covered pond with a friend at a golf course. He became ill, suffered a seizure, and died of heart failure two days later. His friend was also poisoned but recovered. Despite the death not being quick, toxicology of blood and stool samples from both of the boys revealed anatoxin. (Note: I’m a little skeptical that anatoxin is the primary agent responsible for the young man’s death, but medical examiners only need to be 51% sure, so in the absence of any other reasonable cause of death, that’s how it was recorded.) (3)
Anatoxin can be found in cyanobacteria blooms around the world, and on every continent – including Antarctica(!) – and kills indiscriminately. Lake Bogoria, Kenya, experienced a devastating mass fatality in 1999. Home to one of the largest populations of lesser flamingos in the world, Lake Bogoria is home to roughly 500,000 flamingos, which eat about 72 grams (dry weight) of algae per day. That year, extensive mats from cyanobacteria Phormidium terebriformis, Oscillatoria willei, Spirulina subsalsa and Synechococcus bigranulatus took over the lake. Feeding flamingos ingested large amounts of anatoxin, both from ingesting the cyanobacteria and tphe oisoned water, resulting in the deaths of over 30,000 flamingos. (4)
Lake Bogoria by Bob Walker (CC BY-SA-2.5)
Not all algal blooms are the same. We’ve read about algal blooms resulting in shellfish poisonings of the diarrheal, amnesic, paralytic, and neurotoxic types, but now we’re introduced to one that kills quickly, the Very Fast Death Factor known as anatoxin. So if you see a scum-covered pond, lake, or river, it’s best not to go drink from it or play in it. Nature is all around us, and while wonderous, can also be harmful.
References:
- Rose, Earl T. “Toxic Algae in Iowa Lakes.” Proceedings of the Iowa Academy of Science, vol. 60, 1953.
- Osswald, Joana, et al. “Toxicology and Detection Methods of the Alkaloid Neurotoxin Produced by Cyanobacteria, Anatoxin-a.” Environment International 33.8 (2007): pp. 1070–1089.
- Behm, Don. “Coroner Cites Algae in Teen’s Death.” Milwaukee Journal-Sentinel, 5 Sept. 2003.
- Krienitz, L. “Contribution of Hot Spring Cyanobacteria to the Mysterious Deaths of Lesser Flamingos at Lake Bogoria, Kenya.” FEMS Microbiology Ecology 43.2 (2003): 141-48.
Nature's Poisons 
Most interesting. I once had a patient who had severe sudden-onset GI symptoms, fortunately only lasting a few days, occurring after he drank an algae supplement that had been in his refrigerator for a few months. He had taken some when he bought it with no side effects. I always wondered if it could have undergone a toxic bloom; happens in cold mountain lakes, so why not refrigerators? Our lab was uninterested, on grounds that after all he survived.
Why algae solutions were being sold as a supplement is a further interesting question.
Algal supplements are sold quite a lot, one of the best known brands is Spirulina. Most of them are sold in tablet form ,and not as a solution, so I’m stumped about that as well.
Algae is actually very nutritious.
This specific phenomenon happens often in systems close to human settlement because of one thing: Phosphorous. Phosphorous is the limiting factor in aquatic environments which means that this is a key ingredient to life that is often in low quantities but then acts as invasive. Phosphorous is unnecessarily high in fertilizers (Phosphorous is almost never low in terrestrial settings) but when run-off occurs in semi-closed systems like the Puget Sound levels become extremely high. This in turn gives rise to giant Algal blooms which is fancy for – algae quickly become invasive by eating all the phosphorous, creating giant blooms which then eat all the 02 in the water, creating dead zones killing all who enter either through lack of 02 or by creating anatoxin – then the algae die when they have used up the 02.