The results of the investigation of the causes of Minimata disease (MD) by the first MD study group at Kumamoto University School of Medicine have been widely acknowledged in Japan.1 In 1968, the Japanese government officially recognized the disease was caused by human ingestion

of a large amount of methylmercury (Me-Hg)-contaminated fish or shellfish from Minamata Bay and that it injured mainly the nervous system. But it was long unclear that the cause was the huge amount of Me-Hg Selleckchem Navitoclax dumped into Minamata Bay. New facts came to light only after the political solution of MD problems in 1995. Nishimura et al.2,3 reported that large amounts of Me-Hg had been generated by chemical processes of the Chisso Co. acetaldehyde plant in August 1951 and were later dumped directly into Minamata Bay (Fig. 1). The pathogenesis of chronic types of MD was at first considered to be due to brain damage by low-level persistent exposure to Me-Hg.4 However, it was later realized to be the after-effects of high-level Me-Hg intake by the residents around Minamata Bay between 1951 and 1968, because the mercury levels of fish abruptly dropped in 1968 (Fig. 2). Also, the pathogenesis

of selective vulnerability within the cerebral cortex was not clear for a long time. Eto et al.5,6 demonstrated experimentally using common marmosets that edema in the white matter near the deep sulci may contribute to the selective damage of the cerebral cortex. According to new reports over the last decade, medical studies appear Ruxolitinib nmr to have resolved the MD problem. It was in 1953 that MD was first recognized by the medical profession as a mysterious neurological illness occurring in the Minamata Bay area of Kumamoto Prefecture, Kyushu, Japan. The earliest

phase of investigation into this disorder was a personal one; Hosokawa, then Physician-in-chief at the hospital run by the chemical plant later identified as the source of the mercury pollution responsible for the illness, made clear the unique clinical features of the disorder through detailed observation of patients during the period 1953 through 1956, and further suggested the likely Coproporphyrinogen III oxidase involvement of seafood from Minamata Bay in its etiology. This ground-breaking work of Hosokawa should have immediately become widely known but instead remained largely in the form of personal notes mainly due to suppression by his employer. In 1956 when the outbreak was already in an endemic stage, a systematic endeavor to clarify the nature of the disease was initiated. A five-member committee comprising Katsuki (internal medicine), Rokutanda (microbiology), Takeuchi (pathology), Kitamura (public health) and Ozaki (pharmacology), was organized at Kumamoto University School of Medicine.