Comprehensive Chronology of D.I.S. and Related Events in Japan

Chloroquine-Induced SufferingMajor powers use quinone for malaria treatment; quinone is included in the Japanese Pharmacopoeia (1939)
Bayer of Germany synthesizes chloroquine (1934), and American companies used chloroquine as a specific treatment for malaria (1943)

Drug-Induced SMON (Subacute Myelo-Optic Neuropathy)Major powers use quinone for malaria treatment; quinone is included in the Japanese Pharmacopoeia (1939)

Chloroquine-Induced SufferingThe MHW instructs that warnings about chloroquine retinopathy should be added to the package inserts (1969)

Drug-Induced SMON (Subacute Myelo-Optic Neuropathy)[SMON] The MHW launches a research group (1969), and the victims’ group is established by the victims themselves (1969)

Drug-Induced Suffering from Labor-Inducing DrugsAbuse of labor induction by physicians becomes a social problem (1970s–1980s)

Drug-Induced SMON (Subacute Myelo-Optic Neuropathy)Competing hypotheses are proposed regarding the “SMON = clioquinol hypothesis” (Associate Professor Inoue, Kyoto University) and the “SMON = viral hypothesis” (Professor Tamura, University of Tokyo). The MHW bans the use of Clioquinols (1970). Lawsuits are filed against the government and pharmaceutical companies (1971), and settlements begin in various regions (1979).

Drug-Induced Creutzfeldt-Jakob Disease (CJD)Approval of “Lyodura” (1973)

Drug-Induced Muscle ContractureThe Japan Medical Association issues a notice on the measures for muscle contracture (1974). The Japan Pediatric Society issues an apology statement (1976).

Thalidomide-Induced SufferingSettlement is reached between the government and pharmaceutical companies (1974).

Drug-Induced HIV/AIDS (through Blood Products)The National Diet passes a resolution for the “early relief for patients infected with HIV-contaminated blood products” (1988); and lawsuits filed against the government and pharmaceutical companies in the Tokyo and Osaka District Courts (1989)

Drug-Induced Suffering from Labor-Inducing DrugsThe victims’group is established by the victims themselves (1988)

MMR (Measles, Mumps, and Rubella vaccine) Vaccine-Induced SufferingMMR Vaccine is included in the Routine Immunization Schedule (April 1989)

MMR Vaccine-Induced SufferingIn an investigation report by the Maebashi Medical Association (1989), three victim families sued the government and pharmaceutical companies (1993), and MMR vaccinations were temporarily suspended (1993)

Drug-Induced Muscle ContractureSettlement reached with medical institutions and pharmaceutical companies (1990s)

Drug-Induced Suffering from Labor-Inducing DrugsThe victims’group requests that the MHW revise the package inserts; the government responds (1992)

Gefitinib-Induced SufferingClinical trial results show that Iressa has no life-prolonging effect; new patient use is banned in principle in the US (2005); lawsuits against the government and pharmaceutical companies commences in Tokyo and Osaka District Courts (2005)

Thalidomide-Induced SufferingThalidomide is approved as a drug for the treatment of multiple myeloma (2008) and Hansen’s disease (2012)

Gefitinib-Induced SufferingAstraZeneca withdraws the Iressa approval application in the US (2011), Japan limits Iressa insurance coverage to patients with specific genetic mutations (2011), Tokyo and Osaka District Court rulings and appeals (2011), and the Supreme Court dismisses the appeal against the state; the plaintiffs lose (2013)

Inclusion in the National Immunization Program under the Vaccination Law (2013)

HPV Vaccine-induced SufferingFormation of the “All Japan Coordinating Association of HPV Vaccine Sufferers” (2013); Inclusion in the National Immunization Program under the Vaccination Law, followed by a temporary suspension of active vaccination recommendations three months later (2013); Initiation of lawsuits against the government and pharmaceutical companies (2016)