## 1 Introduction
In a study of the food chain in the Pacific and the Caribbean [55], [PERSON] showed that carnivorous fish were always more [PERSON] than herbivorous, detritus, and mollusc-feeding fishes. A detailed analysis of the stomach and intestinal contents of surgeonfishes and parroftishes led him to propose that a benthic organism, most likely a blue-green algae, could be the source of the toxins in CP. The later [PERSON] of ciguotoxicity in the muscle, [PERSON], and viscera of the herbivorous surgeonfish _Ctenochaetus striatus_ in Tahiti supported this hypothesis when Dr [PERSON] began researching ciguatera in French Polynesia in the late 1960s [57]. In 1975, [PERSON] and [PERSON] found low levels of ciguatoroxins in the muscles and viscera of the surgeonfish _Ctenochaetus striatus_ and the grouper _Plectropomus leopardus_[58], using a rapid semi-purification of liposoluble residue known as rapid cold alkali treatment [59]. This confirmed that edible coral fishes can harbour low levels of ciguatoroxins, supporting its accumulation along the food web, as predicted by [PERSON] in 1958 [55]. Their rapid cold alkali treatment allows for defatting using saponification at room temperature of any lipid-soluble residue (LR) solubilized in one volume of 5% KOH in 90% ethanol/water. After 5 min, three volumes of water are added, and the ethanolic fraction is extracted using diethyl ether to give an unsaponifiable fraction containing P-CTXs [59]. A collaboration between Japan and French Polynesia showed that corallivorous _Scarus gibbus_ and carnivorous _Epinephelus microdon_ could also retain ciguotoxins [60; 61]. [PERSON] and his team ([PERSON], [PERSON], [PERSON], [PERSON], [PERSON]) also studied coral covered with a greenish layer collected in the ciguatera-endemic Gambier Islands of French Polynesia. These coral samples were extracted by [PERSON] using acetone in the late 1975, and the dried extract was directly injected into mice or injected after rapid cold alkali treatment [59]. Importantly, these injected mice showed typical specific ciguatoxic signs, including penile symptoms [59], which provided the first evidence that this layer was the source of ciguatoxins [62]. To build on these new findings, the South Pacific Commission (SPC) funded a new mission between the researchers in Tahiti (French Polynesia) and [PERSON] in 1976 to isolate the causative organism of ciguatera. [PERSON] et al. and [PERSON] et al. [63; 64] further characterised the implicated dinoflagellate, which was later named _Gambierdiscus toxicus_ by [PERSON] and [PERSON] [65; 66]. In parallel, [PERSON] first described maitotoxin (MTX), a potent water-soluble toxin found into the gut contents of the surgeonfish _C. striatus_ (called \"maito\" in Tahiti) [67]. Additional experiments initiated in 1975 and 1976 on coral substrate and the viscera of parrotfishes and surgeonfishes suggested that maitotoxin was a marker of the dinoflagellate rather than a precursor of ciguatoxins [62; 68]. This is in line with the observation that different strains of _G. toxicus_ also produce chemically distinct but pharmacologically related MTXs [69; 70; 71; 32; 72; 73; 74; 75; 76; 77]. [PERSON] and [PERSON] also suggested that ciguatoxin production may require an enhancer, which could be another microorganism (e.g., bacteria) associated with the dinoflagellate and/or dead coral [62; 68]. This hypothesis was supported by experimental results [78; 79], and it is in line with the fact that, to our knowledge, gambiertoxin/ciguatoxin production has not been confirmed in axenic cultures. Genetics were also suspected to explain the low percentage of culturable clonal strains of _Gambierdiscus_ that produce detectable levels of gambieroxins/ciguatoxins [77; 80]. Significant strain-dependent differences in the levels and types of ciguatoxins and maitotoxins produced by the same _Gambierdiscus_ species were highlighted [81].