News Release

After hooking toxin behind seafood poisoning, Science researchers may tackle prevention

Peer-Reviewed Publication

American Association for the Advancement of Science (AAAS)

This release is also available in Japanese. The Japanese translation requires Adobe Acrobat Reader with Asian font pack.

The chemical culprit that triggers 20,000 annual cases of seafood poisoning has evaded scientific scrutiny for years because very little of it can be extracted from nature. Now, a team of Japanese researchers has invented a way to make this complex toxin in a laboratory for the first time. The study will be published in the 30 November issue of the journal, Science.

Synthetically producing the toxin responsible for seafood poisoning may fuel future development of more efficient methods to detect infected fish before they hit the dinner plate.

Most cases of ciguatera, or seafood poisoning, occur in subtropical and tropical regions, where fish are most commonly infected. “Because reef fish are increasingly exported to other areas, and ciguateric fish look, taste, and smell normal, ciguatera may become a world-wide health problem,” says Science researcher Masahiro Hirama and colleagues at Tohoku University and CREST, Japan Science and Technology Corporation in Sendai, Japan.

“Currently, there are no rapid and reliable methods of detecting ciguatoxins at fisheries,” Hirama says. Heating, freezing, or drying does not destroy the toxin, either.

The Hirama team’s work will allow scientists to better understand details of how the chemical, ciguatoxin, inflicts damage on humans and to prepare toxin-fighting antibodies to deploy for detection.

Over 400 species of fish are known to transport ciguatera neurotoxins into the human food chain, causing gastrointestinal, neurological, and cardiovascular problems that can last from months to years, sometimes resulting in death, according to the study.

The Science research overcomes the previous challenges of isolating ciguatoxin from nature. Although very potent, the actual amount of collectable toxin is very low in fish, and cultivating natural samples of the chemical proved too unreliable to facilitate public health research.

The complicated and large architecture of the toxin has previously impeded chemists from completing its total synthesis. Hirama stepped up to the challenge when now retired Takeshi Yasumoto of Tohoku University, who isolated and determined the ciguatoxin structure by nuclear magnetic resonance in 1989, asked him to help define the absolute stereostructure of ciguatoxins with synthesis technology.

“[Yasumoto’s] information regarding ciguatoxin attracted my attention…I thought that organic synthetic chemists should challenge this synthesis and could contribute towards the human health and development of biological, medical, and pharmacological studies,” Hirama says.

“After ten years of tackling this, we eventually accomplished the total synthesis and proved the powers of modern organic synthesis and Japanese chemists,” Hirama says. His team assembled two comparably complex fragments, discovered a way to successfully unify them, and then fine-tuned the resulting compound, ciguatoxin CTX3C.

This production technique “will provide a practical supply of ciguatoxins for further studies…. We can now start further studies using synthetic ciguatoxins and related designed chemical molecules.”

Hirama adds, “We are planning to prepare a simple and sensitive kit, like pH papers to measure pH, to detect ciguatoxins by using anti-ciguatoxin antibodies, and ciguatoxin-vaccines, as well,”

New molecular probes can also be created to examine the exact mechanism by which the chemicals latch on and impact the nervous system. Even the toxins themselves, supplied by synthesis, can be quite useful for such studies, according to Hirama. The neurotoxins bind to voltage-sensitive sodium channels of nerves, causing them to remain activated longer than normal.

The chemicals are produced primarily by a species of marine dinoflagellate, Gambierdiscus toxicus, which are one-celled organisms, invisible to the naked eye, that live on macro-algae. The dinoflagellates do not always produce toxins in the wild, and of those that do, some stop production once cultured.

Humans acquire the neurotoxin when they eat fish that have consumed toxic algae or other fish that have accumulated the poison. The ciguatera toxins are structurally similar to but larger and more toxic than the same chemicals associated with red-tide algal blooms. Only a tiny amount -- about 70 nanograms -- causes human illness.

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The other members of the Science team include Tohru Oishi, Hisatoshi Uehara, Masayuki Inoue, Megumi Maruyama, Hiroki Oguri, and Masayuki Satake.

Funders of this research were the Japan Science and Technology Corporation and the Ministry of Education, Culture, Sports Science, and Technology.

A related perspective article in Science is available by István E Markó at Université Catholique de Louvain in Louvain-la-Neuve, Belgium.

For a copy of this research article, please contact the Science media relations team at the American Association for the Advancement of Science News and Information Office, (202) 326-6440 or scipak@aaas.org


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