Determination of the cause of Minamata disease

Investigation of the Cause of Minamata Disease

After May 1, 1956 when the outbreak of Minamata disease was ﬁrstly discovered, Study Group of Kumamoto University reported that the cause of the disease was intoxication caused by eating ﬁshes and shellﬁshes contaminated with a kind of heavy metal on Nov. 3, 1956.
But it took a long time to determine the cause of the strange disease as a methylmercury poisoning.
Meanwhile, the number of patients continued to grow because the national and prefectural governments, despite the suspicion pointing to fish and shellfish from Minamata Bay, did not ban fishing or take other such measures, and because Chisso, which by 1959 had realized that the wastewater out of its factory was the cause, continued letting it flow out.

Results of the Study done by Kumamoto University Study Group

Inferring that the cause of the disease might rest with fish and shellfish from Minamata Bay, the Research Group started, around November 1956, experiments of having cats eat fish and shellfish from Minamata Bay. In the following year, Director Ito of the Minamata Health Center, who was collaborating with Professor Takeuchi to conduct the experiments, had a result showing that cats had developed symptoms, a clear indication that fish and shellfish caught in Minamata Bay was the cause of Minamata disease. Professor Sera also corroborated that a healthy cat, having been sent to the area where Minamata disease had occurred and been kept there, would develop Minamata disease symptoms.
The Research Group then proceeded to work on identifying the substance being the cause of Minamata disease, which turned out, however, to be a slow and difficult task, for more than 10 types of harmful substances were detected in the sludge and fish and shellfish collected from Minamata Bay.
It was in 1959 that the Research Group placed their focus on organic mercury, which they did after Professor Takeuchi and (then) Assistant Professor Tokuomi reported on the organic mercury theory, having noticed from foreign literature that there were similarities between the symptoms of Minamata disease and those of mercury poisoning. On July 22 of the same year, the Research Group made their opinion public that organic mercury was likely the cause of Minamata disease, based on their findings that cats having been fed organic mercury had developed Minamata disease symptoms, coupled with evidence gained from an analysis conducted by Professor Kitamura that mercury was flowing out of Chisso's discharge outlets.
This was met with opposition, arguing that the possibility of organic mercury being found in Minamata Bay would be unthinkable. The reason was the fact that while inorganic mercury had been used in the factory, no organic mercury had been used. As, back then, there was no technology capable of analyzing organic mercury accurately, it was very difficult to confirm its presence. In November 1961, however, Professor Uchida reported on his achievement of extracting a methylmercury compound (a type of organic mercury) from shellfish (hormomya mutabillis) from Minamata Bay, followed by another report issued in August 1962 by Professor Irukayama that a methylmercury compound had also been extracted from catalyst residues collected from the acetaldehyde manufacturing equipment.

Chronology of research in early days

Year	Occurrences	Total count of patients confirmed
1951	[Society] ・Deaths, deformations and other abnormalities in fish and shellfish in Minamata Bay began to be noticed [Subject company] ・Replaced manganese dioxide with (crude) ferrous sulphate for use as a co-catalyst for acetaldehyde synthesis
1953	[Society] ・Around this time, the first officially-found patient developed the symptoms [Subject company] ・Adopted a vacuum evaporation and vacuum distillation method for acetaldehyde production
1956	[Society] ・(1954 to 1959) In addition to cats developing symptoms, incidents of serious damage emerged one after another, including clinging shellfish and seaweeds dying and disappearing and fish floating to the surface [Subject company] ・A new plant was completed, followed by a series of incidents (abnormal increases of effluents) ・Company hospital director (Dr. Hosokawa) reported to the Minamata Health Center on the appearance of an illness of an unknown cause [Public authorities] ・(May 1) Minamata disease detected officially ・November: Science Research Team, Ministry of Health (hereinafter indicated as the "Scientific Research Team") established ・52 persons officially recognized by Unknown Disease Committee as being afflicted with Minamata (unknown) disease [Kumamoto University] ・(August) School of Medicine formed Minamata Unknown Disease Research Group ・(August 30) "Case study patient" program (under which patients would agree to cooperate in the determination of the cause in exchange for medical cost waiver) launched for the first time ・(November) First report session: Reported that the "unknown disease" was some type of heavy metal poisoning through fish and shellfish intake and was not contagious Pointed out that damage to the central nervous system was the main symptom	52
1957	[Society] ・Pacific oyster found to have died abruptly (Kumamoto Prefecture Fisheries Experiment Station) [Subject company] ・Patients' lifestyles and clinical symptoms surveyed (by Dr. Hosokawa and several other researchers) ・(May) Formed an organization engaged to study the Minamata unknown disease ・(May) Cat experiments begun at the company hospital ・Wastewater, seawater, bottom sediments, fish, shellfish, etc. surveyed for contamination (mainly manganese) ・(December) Thallium and selenium detected in the sludge (reply to inquiries from the Kumamoto University Research Group) [Public authorities] ・(January) First report session held by the Scientific Research Team (fish and shellfish found to be the medium for heavy metal poisoning, while its mechanism remained unknown) (written report issued in March) ・Hyakuken Port dredged (Kumamoto Prefecture) ・Director Ito of the Minamata Health Center: (April) Cat found to have developed symptoms 10 days after being fed fish and shellfish from Minamata Bay ・(July) Fourth report session held by the Scientific Research Team Factory effluents suspected to be involved ・Based on the findings from cat experiments, etc., fish and shellfish from Minamata Bay assumed to be the cause, while the poisoning substance remained to be determined (Kumamoto Prefecture Hygiene Department) ・Kumamoto Prefecture Hygiene Department: (August) Inquiries made with the Ministry of Health as to whether the sale of fish and shellfish from Minamata Bay should be banned under the Food Sanitation Act ↓ ・(September) Ministry of Health replied to Kumamoto Prefecture that the Food Sanitation Act was not applicable, implications being that fishing should not be banned ・(October) Report given by Scientific Research Team leader Matsui at an academic conference: While several salts, including manganese, copper, selenium and thallium, were named as the possible cause of poisoning, no evidence was found to sufficiently support that any of those substances was the cause. Thus far, mercury had not been looked at as a possible cause (the report was issued in December) [Kumamoto University] ・(February) Second report session: Concluded that measures are needed to ban fishing in Minamata Bay	64
1958	[Society] ・The term "Minamata disease" took root in the mass media ・(October) Report given about abrupt deaths of Manila clams, oysters, etc. and the absence of bottom-living larvae and plankton in Hyakuken Port (Kumamoto Prefecture Fisheries Experiment Station) [Subject company] ・Five children with polio-like conditions (who would later be found to have fetal Minamata disease) examined by Dr. Hosokawa ・Production soared as a result of the completion of acetic acid equipment and continuous stock solution oxidation system ・(July) "Our View on Minamata Unknown Disease" released Claim made to the Ministry of Health that until the substance causing the disease is identified, the factory wastewater should not be considered suspect ・(September) Acetaldehyde discharge channel changed from Hyakuken Port to the Minamata River estuary via the Hachiman Pool [Public authorities] ・February: Results of analysis of the sludge in the Minamata factory examined by the Science Research Team at its report session Confirmed that the Minamata factory was generating the disease-causing substance; experimental reproduction was set as a future task [Kumamoto University] ・Theory that selenium was the most likely suspect (28th Hygiene Conference) ・Thallium theory presented by Professor Miyagawa (Conference on Psychiatry and Neurology) ・(July) Professor Takeuchi commented at a meeting with Shin-Nippon Chisso that it was difficult to determine categorically that selenium, thallium or manganese was the cause [Other researchers] ・(September) Possibility of organic mercury poisoning indicated by Dr. MacAlpine in an academic journal (co-authored with Dr. Araki)	68
1959	[Society] ・Patient found among residents of Hachiman (Minamata River estuary) for the first time (March), after which cases appeared one after another ・A large number of cats in Yunoura-machi, Ashikita-gun found to have developed symptoms ・Starting in February, cats in Shishijima Island found to have developed symptoms (18 cats in one month) ・(June) Patient found in Izumi, marking the start of spreads southwards from the area in which cases first appeared ・(September) Cats in Izumi, having been fed dried shellfish, developed symptoms ・Fisherman uproar (2,000 fishermen gathered and, after making a petition with the national parliamentary investigation team, broke into the factory) ; more than 100 people injured ・(December) Consolation payment agreement made [Subject company] ・(July) Dr. Hosokawa began experiments, with cat No. 400 among the subjects, using effluents from the acetaldehyde and acetic acid manufacturing processes ・(August) Written opposition against the organic mercury theory submitted to the Kumamoto prefectural assembly Opposing the organic mercury theory, drawing on the failure to extract alkyl mercury from fish and shellfish, and also arguing that there was neither fact nor literary record that suggests organic mercury could be generated in the production process ・(October) Cat No. 400 (directly fed effluent-added food) developed symptoms ・Wastewater discharges in the direction of the Minamata River estuary stopped; discharge channel changed back to Hyakuken Port ・(November) Written opposition, "Our view on the "theory of organic mercury" being the substance causing Minamata disease," brought to the national parliamentary investigation team ・(November) Dr. Hosokawa instructed by the company to stop his cat experiments; new experiments involving directly feeding cats effluent-added food thus stopped ・(December)Wastewater treatment equipment (Cyclator) Completed (it had no effect on methylmercury removal) [Public authorities] ・(October) Food Sanitation Investigation Groups Joint Committee, Ministry of Health; organic mercury theory reported by the Minamata Food Poisoning Subcommittee ・(October) Ministry of International Trade and Industry instructed Shin-Nippon Chisso to decommission the Minamata River estuary discharge channel and finish building the wastewater treatment equipment by the end of the year ・(November) National parliamentary investigation team visited Minamata for inspection ・(November) Food Sanitation Investigation Groups Standing Committee Minamata Food Poisoning Subcommittee dissolved after presenting a view that the case relates to a poison disease principally caused by organic mercury compounds, the symptom of which was damage mainly to the central nervous system resulting from a large intake of fish and shellfish from Minamata Bay ・(December) Minamata Patient Diagnosis Council (Public Health Bureau, Ministry of Health) [Kumamoto University] ・(March) Third report issued Mentioned that a large number of children have been found to show polio-like symptoms (Professor Kitamura) ・(July) Research Group report session Concluded that "mercury draws significant attention as a poisonous substance that has contaminated fish and shellfish" (Takeuchi and Tokuomi bringing forth the organic mercury theory) ・(August) Professor Irukayama collected mercury sludge from the acetic acid equipment [Other researchers] ・Professor Kiyoura of Tokyo Institute of Technology (August) Cautious view on the organic mercury theory ・(September) Director Oshima of the Japan Chemical Industry Association (JCIA) questioned the organic mercury theory and supported a theory pointing to some explosive material	68
1960	[Subject company] ・(August) Dr. Hosokawa resumed experiments involving directly feeding cats effluent-added food for possible development of symptoms [Public authorities] ・Minamata Disease Comprehensive Investigation and Research Liaison Council established First session held in February ・(February) Institute of Health Sciences, Kumamoto Prefecture began testing mercury levels in hairs of people living in Yatsushiro Sea coastal areas ・(May) Kagoshima Prefecture began testing mercury levels in hairs of people living in Izumi, Komenotsu, Azumacho (Nagashima), etc. [Kumamoto University] ・(February) Professor Kitamura noticed the utility of mercury levels in hair and studied patients' hair ・(April) 57th Conference on Psychiatry and Neurology Organic mercury theory and thallium theory presented and discussed; organic mercury theory gained support ・(September) Professor Miyakawa deceased; thallium theory faded away ・(September) Professor Uchida succeeded in crystallizing a sulfur-containing organic mercury compound from Manila clams from Minamata Bay [Other researchers] ・(February) Dr. Kurland (National Institute of Health, U.S.A.) supported the organic mercury theory, also commenting that Cyclator was not useful for harmful substance removal ・(April) JCIA Tamiya Committee set up ・(April) Liaison Council second meeting; poisonous amine theory presented by Professor Kiyoura	87
1961	[Subject company] ・(July) Alkyl mercury compound (organic mercury) confirmed to be contained in the wastewater discharge ・(December) Methylmercury extracted from effluents and crystallized [Kumamoto University] ・(June) Professor Yoshitaka Harada presented, for the first time, the true picture of fetal Minamata disease at a Kyushu regional section meeting of the Pediatric Society ・(October) Professor Irukayama and others presented in Kumamoto Medical Journal that mercury in fish and shellfish got taken in in the form of organic mercury ・(November) Professor Uchida made a presentation at an academic conference on the crystallization of methylmercury sulfide [Other researchers] ・(June) Decomposed amine theory proposed by Professor Kiyoura (Journal of the Medical Society of Toho University)	87
1962	[Kumamoto University] ・(August) Professor Irukayama and others successfully extracted methylmercury chloride from catalyst residues
1965	[Society] ・Minamata disease patients found in Niigata; an official announcement by Niigata Prefecture came out in June	26 in Niigata
1967	[Public authorities] ・(August) Ministry of Health determined the cause of Niigata Minamata disease to be pollution resulting from methylmercury compounds, produced incidentally from the acetaldehyde manufacturing process in the Kanose factory of Showa Denko, that entered into the food chain	27 in Niigata
1968	[Subject company] ・Stopped the operation of the acetaldehyde manufacturing process [Public authorities] ・(September) Cabinet consensus Concluded that the cause of the disease was methylmercury compounds having been produced incidentally in the acetaldehyde and acetic acid manufacturing processes in the Minamata factory of Chisso	35 in Niigata

1951
[Society]: ・Deaths, deformations and other abnormalities in fish and shellfish in Minamata Bay began to be noticed
[Subject company]: ・Replaced manganese dioxide with (crude) ferrous sulphate for use as a co-catalyst for acetaldehyde synthesis

1953
[Society]: ・Around this time, the first officially-found patient developed the symptoms
[Subject company]: ・Adopted a vacuum evaporation and vacuum distillation method for acetaldehyde production

1956
[Society]: ・(1954 to 1959) In addition to cats developing symptoms, incidents of serious damage emerged one after another, including clinging shellfish and seaweeds dying and disappearing and fish floating to the surface
[Subject company]: ・A new plant was completed, followed by a series of incidents (abnormal increases of effluents); ・Company hospital director (Dr. Hosokawa) reported to the Minamata Health Center on the appearance of an illness of an unknown cause
[Public authorities]: ・(May 1) Minamata disease detected officially; ・November: Science Research Team, Ministry of Health (hereinafter indicated as the "Scientific Research Team") established; ・52 persons officially recognized by Unknown Disease Committee as being afflicted with Minamata (unknown) disease
[Kumamoto University]: ・(August) School of Medicine formed Minamata Unknown Disease Research Group; ・(August 30) "Case study patient" program (under which patients would agree to cooperate in the determination of the cause in exchange for medical cost waiver) launched for the first time; ・(November) First report session:
Reported that the "unknown disease" was some type of heavy metal poisoning through fish and shellfish intake and was not contagious
Pointed out that damage to the central nervous system was the main symptom; Total count of patients confirmed: 52

1957
[Society]: ・Pacific oyster found to have died abruptly (Kumamoto Prefecture Fisheries Experiment Station)
[Subject company]: ・Patients' lifestyles and clinical symptoms surveyed (by Dr. Hosokawa and several other researchers); ・(May) Formed an organization engaged to study the Minamata unknown disease; ・(May) Cat experiments begun at the company hospital; ・Wastewater, seawater, bottom sediments, fish, shellfish, etc. surveyed for contamination (mainly manganese); ・(December) Thallium and selenium detected in the sludge (reply to inquiries from the Kumamoto University Research Group)
[Public authorities]: ・(January) First report session held by the Scientific Research Team (fish and shellfish found to be the medium for heavy metal poisoning, while its mechanism remained unknown) (written report issued in March); ・Hyakuken Port dredged (Kumamoto Prefecture); ・Director Ito of the Minamata Health Center:
(April) Cat found to have developed symptoms 10 days after being fed fish and shellfish from Minamata Bay; ・(July) Fourth report session held by the Scientific Research Team
Factory effluents suspected to be involved; ・Based on the findings from cat experiments, etc., fish and shellfish from Minamata Bay assumed to be the cause, while the poisoning substance remained to be determined (Kumamoto Prefecture Hygiene Department); ・Kumamoto Prefecture Hygiene Department:
(August) Inquiries made with the Ministry of Health as to whether the sale of fish and shellfish from Minamata Bay should be banned under the Food Sanitation Act; ↓; ・(September) Ministry of Health replied to Kumamoto Prefecture that the Food Sanitation Act was not applicable, implications being that fishing should not be banned; ・(October) Report given by Scientific Research Team leader Matsui at an academic conference:
While several salts, including manganese, copper, selenium and thallium, were named as the possible cause of poisoning, no evidence was found to sufficiently support that any of those substances was the cause. Thus far, mercury had not been looked at as a possible cause (the report was issued in December)
[Kumamoto University]: ・(February) Second report session:
Concluded that measures are needed to ban fishing in Minamata Bay; Total count of patients confirmed: 64

1958
[Society]: ・The term "Minamata disease" took root in the mass media; ・(October) Report given about abrupt deaths of Manila clams, oysters, etc. and the absence of bottom-living larvae and plankton in Hyakuken Port (Kumamoto Prefecture Fisheries Experiment Station)
[Subject company]: ・Five children with polio-like conditions (who would later be found to have fetal Minamata disease) examined by Dr. Hosokawa; ・Production soared as a result of the completion of acetic acid equipment and continuous stock solution oxidation system; ・(July) "Our View on Minamata Unknown Disease" released
Claim made to the Ministry of Health that until the substance causing the disease is identified, the factory wastewater should not be considered suspect; ・(September) Acetaldehyde discharge channel changed from Hyakuken Port to the Minamata River estuary via the Hachiman Pool
[Public authorities]: ・February: Results of analysis of the sludge in the Minamata factory examined by the Science Research Team at its report session
Confirmed that the Minamata factory was generating the disease-causing substance; experimental reproduction was set as a future task
[Kumamoto University]: ・Theory that selenium was the most likely suspect (28th Hygiene Conference); ・Thallium theory presented by Professor Miyagawa (Conference on Psychiatry and Neurology); ・(July) Professor Takeuchi commented at a meeting with Shin-Nippon Chisso that it was difficult to determine categorically that selenium, thallium or manganese was the cause
[Other researchers]: ・(September) Possibility of organic mercury poisoning indicated by Dr. MacAlpine in an academic journal (co-authored with Dr. Araki); Total count of patients confirmed: 68

1959
[Society]: ・Patient found among residents of Hachiman (Minamata River estuary) for the first time (March), after which cases appeared one after another; ・A large number of cats in Yunoura-machi, Ashikita-gun found to have developed symptoms; ・Starting in February, cats in Shishijima Island found to have developed symptoms (18 cats in one month); ・(June) Patient found in Izumi, marking the start of spreads southwards from the area in which cases first appeared; ・(September) Cats in Izumi, having been fed dried shellfish, developed symptoms; ・Fisherman uproar (2,000 fishermen gathered and, after making a petition with the national parliamentary investigation team, broke into the factory) ; more than 100 people injured; ・(December) Consolation payment agreement made
[Subject company]: ・(July) Dr. Hosokawa began experiments, with cat No. 400 among the subjects, using effluents from the acetaldehyde and acetic acid manufacturing processes; (August) Written opposition against the organic mercury theory submitted to the Kumamoto prefectural assembly
Opposing the organic mercury theory, drawing on the failure to extract alkyl mercury from fish and shellfish, and also arguing that there was neither fact nor literary record that suggests organic mercury could be generated in the production process; ・(October) Cat No. 400 (directly fed effluent-added food) developed symptoms; ・Wastewater discharges in the direction of the Minamata River estuary stopped; discharge channel changed back to Hyakuken Port; ・(November) Written opposition, "Our view on the "theory of organic mercury" being the substance causing Minamata disease," brought to the national parliamentary investigation team; ・(November) Dr. Hosokawa instructed by the company to stop his cat experiments; new experiments involving directly feeding cats effluent-added food thus stopped; ・(December)Wastewater treatment equipment (Cyclator)
Completed (it had no effect on methylmercury removal)
[Public authorities]: ・(October) Food Sanitation Investigation Groups Joint Committee, Ministry of Health; organic mercury theory reported by the Minamata Food Poisoning Subcommittee; ・(October) Ministry of International Trade and Industry instructed Shin-Nippon Chisso to decommission the Minamata River estuary discharge channel and finish building the wastewater treatment equipment by the end of the year; ・(November) National parliamentary investigation team visited Minamata for inspection; ・(November) Food Sanitation Investigation Groups Standing Committee
Minamata Food Poisoning Subcommittee dissolved after presenting a view that the case relates to a poison disease principally caused by organic mercury compounds, the symptom of which was damage mainly to the central nervous system resulting from a large intake of fish and shellfish from Minamata Bay; ・(December) Minamata Patient Diagnosis Council (Public Health Bureau, Ministry of Health)
[Kumamoto University]: ・(March) Third report issued
Mentioned that a large number of children have been found to show polio-like
symptoms (Professor Kitamura); ・(July) Research Group report session
Concluded that "mercury draws significant attention as a poisonous substance that has contaminated fish and shellfish" (Takeuchi and Tokuomi bringing forth the organic mercury theory); ・(August) Professor Irukayama collected mercury sludge from the acetic acid equipment
[Other researchers]: ・Professor Kiyoura of Tokyo Institute of Technology
(August) Cautious view on the organic mercury theory; ・(September) Director Oshima of the Japan Chemical Industry Association (JCIA) questioned the organic mercury theory and supported a theory pointing to some explosive material; Total count of patients confirmed: 68人

1960
[Subject company]: ・(August) Dr. Hosokawa resumed experiments involving directly feeding cats effluent-added food for possible development of symptoms
[Public authorities]: ・Minamata Disease Comprehensive Investigation and Research Liaison Council established
First session held in February; ・(February) Institute of Health Sciences, Kumamoto Prefecture began testing mercury levels in hairs of people living in Yatsushiro Sea coastal areas; ・(May) Kagoshima Prefecture began testing mercury levels in hairs of people living in Izumi, Komenotsu, Azumacho (Nagashima), etc.
[Kumamoto University]: ・(February) Professor Kitamura noticed the utility of mercury levels in hair and studied patients' hair; ・(April) 57th Conference on Psychiatry and Neurology
Organic mercury theory and thallium theory presented and discussed; organic mercury theory gained support; ・(September) Professor Miyakawa deceased; thallium theory faded away; ・(September) Professor Uchida succeeded in crystallizing a sulfur-containing organic mercury compound from Manila clams from Minamata Bay
[Other researchers]: ・(February) Dr. Kurland (National Institute of Health, U.S.A.) supported the organic mercury theory, also commenting that Cyclator was not useful for harmful substance removal; ・(April) JCIA Tamiya Committee set up; ・(April) Liaison Council second meeting; poisonous amine theory presented by Professor Kiyoura; Total count of patients confirmed: 87人

1961
[Subject company]: ・(July) Alkyl mercury compound (organic mercury) confirmed to be contained in the wastewater discharge; ・(December) Methylmercury extracted from effluents and crystallized
[Kumamoto University]: ・(June) Professor Yoshitaka Harada presented, for the first time, the true picture of fetalpediatric Minamata disease at a Kyushu regional section meeting of the Pediatric Society; ・(October) Professor Irukayama and others presented in Kumamoto Medical Journal that mercury in fish and shellfish got taken in in the form of organic mercury; ・(November) Professor Uchida made a presentation at an academic conference on the crystallization of methylmercury sulfide
[Other researchers]: ・(June) Decomposed amine theory proposed by Professor Kiyoura (Journal of the Medical Society of Toho University); Total count of patients confirmed: 87人

1962
[Kumamoto University]: ・(August) Professor Irukayama and others successfully extracted methylmercury chloride from catalyst residues

1965
[Society]: ・Minamata disease patients found in Niigata; an official announcement by Niigata Prefecture came out in June; Total count of patients confirmed: 26 in Niigata

1967
[Public authorities]: ・(August) Ministry of Health determined the cause of Niigata Minamata disease to be pollution resulting from methylmercury compounds, produced incidentally from the acetaldehyde manufacturing process in the Kanose factory of Showa Denko, that entered into the food chain; Total count of patients confirmed: 27 in Niigata

1968
[Subject company]: ・Stopped the operation of the acetaldehyde manufacturing process
[Public authorities]: ・(September) Cabinet consensus
Concluded that the cause of the disease was methylmercury compounds having been produced incidentally in the acetaldehyde and acetic acid manufacturing processes in the Minamata factory of Chisso; Total count of patients confirmed: 35 in Niigata

Medical Treatment of Minamata Disease

Treatments at the early stages

1. Detection of the route of methylmercury exposure and its exclusion

2. Promotion of methylmercury excretion

① Administration of chelating agents: Chemical trapping of methylmercury and excretion via urine
② Administration of SH-compounds having high aﬃnity for methylmercury: oral administration of thiol resin in order to inhibit re-absorption of methylmercury from intestines
③ Hemodialysis with a SH-compounds L-cysteine
④ Blood exchange

3. Administration of antioxidants

It has been clarified one of the causes of methylmercury-induced cellular damage is the increase in reactive oxygen species in tissue cells. Researches are conducted on the use of antioxidants, e.g., vitamin E, which eliminate reactive oxygen species, in addition to excretion treatment.

4. Treatment of symptoms

Since there is currently no definitive cure for Minamata disease, symptomatic therapies are performed.

Treatments at the chronic stages

1. Rehabilitation

Physical therapy and occupational therapy are conducted in order to improve or maintain physical functions. As fetal Minamata disease patients have recently shown progressive impairment in ambulation and dysphagia, they are treated with gait training using, among other things, belt electrode skeletal muscle electrical stimulation (B-SES), HAL (hybrid assistive limb) Single Joint and an unpowered walking assist clutch, as well as swallowing exercises using a combined low-frequency therapy device.

Rehabilitation exercises for patients with impaired ambulation
Swallowing rehabilitation exercises using a combined low-frequency therapy device

2. Treatment of symptoms

In addition to drug therapies to reduce symptoms, e.g., muscle cramps, involuntary movement and abnormal muscle tonus, state-of-the-art therapeutic treatment has been tried in a fashion suited to the symptom. For detailed information, please read the brochure that can be found on our website, "Strides in neurological disorder treatment: Pursuing better basic activities of daily living in Minamata disease patients."

Table: Therapeutic methods for Minamata disease symptoms

Symptom	Therapy
Pain	Magnetic stimulation treatment; spinal stimulation therapy
Tension in limb muscle tissue	Botulinum toxin therapy; intrathecal baclofen therapy; magnetic stimulation treatment
Tremor	Deep brain stimulation