In 1955 a mysterious disease, in some respects resembling polio, made its appearance in Japan. The symptoms were a combination of diarrhea, internal bleeding and various signs of nerve degeneration.

By 1959 the disease had increased in incidence to epidemic proportions and over the next five years there occurred seven major regional outbreaks in a number of populated districts. Many outbreaks were centered around hospitals--places notorious for spreading disease--with the annual peak occurring in late summer, hinting at an infection spread by insects. The illness appeared to be contagious, but at the same time there were indications to the contrary--patients did not display the symptoms typically associated with infections, such as certain blood abnormalities, fevers or rashes. Despite these anomalies, all investigations focused on identifying the virus responsible.

By 1964 the epidemic had worsened and new symptoms, including blindness, were occurring. Some patients died. At the 61st general meeting of the Japanese Society of Internal Medicine in May of 1964, the disease was given a formal name: "Sub-acute Myelo-Optic Neuropathy"--SMON.

In 1964, the Olympic Games were to be held in Japan and the Japanese Government, now very concerned, launched a formal commission under the leadership of a medical doctor, Professor Magojiro Maekawa of Kyoto University, to investigate the epidemic. The commission was formally addressed to the task of identifying the virus responsible for SMON.

As the search for the virus continued fruitlessly, it was drawn to the commission's attention that all the SMON patients had been medically treated for diarrhea, about half taking the drug Enterovioform, and the other half taking a drug called Ernaform. Suspicion naturally arose that these drugs could be contributing to the SMON problem, but it was argued that two different drugs could not cause the same disease. And besides, the conviction that SMON was caused by a virus was too firmly entrenched.

The epidemic continued to progress and in 1967 an alarming new outbreak flared up in Okayama Province. Dozens of elderly women, and some men, were hospitalized, and the numbers were increasing.

In 1969, the Japanese Ministry of Health and Welfare re-formed the SMON Research Commission, with ten times the funding provided previously, to step up the efforts to discover the feared virus threatening the entire country. Ignoring the evidence that perhaps SMON was not infectious at all, the search was extended to include bacteria as possible suspects. The intensified effort achieved nothing.

Eventually, the head virologist of the commission, Professor Reisaku Kono, while still holding on to the virus theory, nevertheless decided all possibilities should be investigated, and appointed epidemiologist Dr Itsuzo Shigomatsu to conduct a nationwide survey of all possible risk factors.

By 1971, with the virus hunt at a dead end, the number of people hospitalized in the Okayama Province accounted for about three per cent of the province's population.

Though most of the research still focused on finding "the" virus, other scientists had been looking elsewhere. One, a pharmacologist, Dr Hiroben Beppu, had in 1969 independently noted the evidence previously rejected by the commission, that SMON victims had received treatment for diarrhea with a number of drugs. Upon investigation, these different drugs turned out not to be different at all; they were all made of a substance called Clioquinol but marketed under different brand names and freely available.