The Cruel Irony of Saxitoxin

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It was summer of 1997 at Cape Blanc on the western coast of Africa and some two hundred monk seals, nearly two-thirds of the population in the region, lay dead (1, 2). The cause of death was saxitoxin, a highly potent neurotoxin, whose existence is one of Nature’s cruelest ironies. Saxitoxin is a chemical compound, an alkaloid to be precise, that binds to sodium and potassium channels in the brain and muscle (3). This binding obstructs the flow of sodium and potassium ions across the cell membrane, impedes the ability of brain cells and muscle cells to send electrical signals, and can cause death by respiratory failure (3). Certain species of marine invertebrates and fish can accumulate saxitoxin to high levels and then pass it on to their predators. A possible mechanism for this is a difference in the sodium and potassium channels between predators and prey. Interestingly, some species of clam have a mutation in a single amino acid of their sodium channels that makes them resistant to saxitoxin (4), to the detriment of many animals up the food chain, including monk seals and humans. Ecologists estimate that during the fateful summer of 1997, the Cape Blanc monk seals could have been ingesting nearly lethal doses of saxitoxin every day from the fish they consumed (2). And every year, seafood contaminated with saxitoxin kills nearly 300 people and sickens another 1700 (3).

Where does saxitoxin come from? The villains in this story are marine microorganims called dinoflagellates. These microorganisms belong to the kingdom Protista, the dusty attic of taxonomy where biologists place eukaryotic life forms that they really don’t understand. Dinoflagellates are about as closely related to humans as to plants and fungi and incredibly diverse within themselves. About 4000 species have been described, 90% of which live in the world’s oceans and survive either by preying on other single-celled organisms or by doing photosynthesis (5). Most of these species do not produce saxitoxin but do have other curious characteristics, like genomes up to 100 times larger than the human genome, permanently condensed chromosomes in all stages of the life cycle (instead of just during cell division, like in other eukaryotes), and chloroplasts acquired independently of land plants (6). Three genera of dinoflagellates that do produce saxitoxin, Gymnodinium, Pyrodinium, and Alexandrium, get consumed by filter-feeding fish and marine invertebrates that effectively concentrate the poison in their viscera (2, 3). The monk seals at Cape Blanc had the misfortune to be near a bloom of Gymnodinium catenatum and possibly Pyrodinium bahamense (2). Such blooms occur seasonally and may account for other unexplained mass mortalities of marine wildlife (2), though, luckily for humans, many countries have monitoring programs for edible mussels, clams, gastropods, crustaceans, and fish that minimize public health risk (3).

Why do dinoflagellates produce saxitoxin? It is unlikely that they intend to kill marine mammals because the saxitoxin-producing species are photosynthetic (7). Arguably, they would derive no benefit from killing high-level predators in their ecosystems and may even be harmed by an increase in lower-level predators that would result. The large size of dinoflagellate genomes, the difficulty of culturing dinoflagellates in the lab, and their extreme divergence from all organisms with sequenced genomes makes genomic and evolutionary studies of saxitoxin production in dinoflagellates challenging, and information is incomplete (8). The most popular and widely studied hypothesis is that saxitoxin deters the immediate predators of photosynthetic dinoflagellates, such as cocepods and mollusks (3). However, evidence is inconclusive because though saxitoxin production correlates with decreased consumption of dinoflagellates by cocepods, many studies have found no effect of saxitoxin on the survival of mollusks, and other studies found that even dinoflagellate species that do not produce saxitoxin could kill their predators by an as-yet-unidentified mechanism (3). Another hypothesis is that saxitoxin acts as a pheromone and regulates mating and other social behavior in dinoflagellate colonies, though any hypothesis that proposes a non-toxic role for saxitoxin must account for how dinoflagellates that do not produce it perform the same tasks (3). Nonetheless, at present, it is a good bet that dinoflagellates use saxitoxin for their own purposes and that its effect on the brain is a cruel irony.

 Sources

  1. The IUCN Red List of Threatened Species. http://www.iucnredlist.org/details/13653/0
  2. Reyero M et al (1999). Evidence of Saxitoxin Derivatives as Causative Agents in the 1997 Mass Mortality of Monk Seals in the Cape Blanc Peninsula. Natural Toxins. 7: 311-315. Open access.
  3. Cusick KD and GS Sayler (2013). An Overview on the Marine Neurotoxin, Saxitoxin: Genetics, Molecular Targets, Methods of Detection and Ecological Functions. Marine Drugs. 11: 991-1018. Open access.
  4. Bricelj VM et al (2005). Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSP. Nature 434:763-767. Paywall.
  5. Dinoflagellates. Smithsonian Museum of Natural History. http://www.mnh.si.edu/highlight/sem/dinoflagellates.html
  6. Wisecaver JH and JD Hackett (2013). Dinoflagellate Genome Evolution. Annual review of microbiology. 65: 369-387. Paywall.
  7. Algae and Human Affairs edited by CA Lembi and JR Waaland and published in 1989.
  8. Hackett JD et al (2013). Evolution of saxitoxin synthesis in cyanobacteria and dinoflagellates. Molecular biology and evolution. 30: 70-78. Open access.