THE SMON FIASCOBy Peter H.
Duesberg & Bryan J.
Ellison
Inventing the AIDS Virus 1996
Blaming non-infectious diseases on infectious microbes has
occurred many times before. Hidden in foreign-language materials and
the footnotes of obscure sources lies the story of SMON, a
frightening disease epidemic that struck Japan while the war on
polio was accelerating in the 1950s. In many ways, SMON anticipated
the later AIDS epidemic. For fifteen years the syndrome was
mismanaged by the Japanese science establishment, where virtually
all research efforts were controlled by virus hunters. Ignoring
strong evidence to the contrary, researchers continued to assume the
syndrome was contagious and searched for one virus after another.
Year after year the epidemic grew, despite public health measures to
prevent the spread of an infectious agent. And in the end, medical
doctors were forced to admit that their treatment had actually
caused SMON in the first place. Once the truth about SMON could no
longer be ignored, the episode dissolved into lawsuits for the
thousands of remaining victims. This story has remained untold
outside of Japan, ignored as being too embarrassing for the virus
hunters. It deserves to be told in full here.
The patient was middle aged, suffering from a mysterious nerve
disorder that had already paralyzed both her legs. Reisaku Kono was
there to observe the victim because of his work studying poliovirus,
which in a few infected individuals would break into the central
nervous system, causing progressive paralysis and sometimes a slow,
miserable, death. While the condition he examined that day in 1959
was not polio, it bore a certain resemblance to it. And the
suspicion was growing that this, too, could be the result of some
undiscovered virus, perhaps one similar to poliovirus.
Kono was visiting the patient at the hospital affiliated with Mie
University's medical school. Hiroshi Takasaki, a professor of
medicine at the university, told Kono about a number of these cases
he had recently seen at the hospital. They now realized they were
facing an outbreak of something new, not just a minor mystery that
doctors would catalog and forget. Just the previous year, medical
Professor Kenzo Kusui had published a report of another such case in
central Japan: The patient had suffered a similarly strange
combination of intestinal problems, manifesting as internal bleeding
and diarrhea, with symptoms of nerve degeneration. This illness,
stomach pains or diarrhea followed by nerve damage, had been noticed
in a few isolated cases as early as 1955, but was now turning into a
local epidemic.
More published reports began accumulating after Kono's visit to
the hospital. The next five years saw seven major regional epidemics
of the new polio-like syndrome, with the annual number of new cases
increasing from several dozen in 1959 to 161 victims by 1964 - an
alarming rate for those small areas. Scientists jumped to
conclusions, believing they had every reason to assume the disease
was infectious. Just its sudden appearance was enough evidence to
convince them. The disease also broke out in clusters around
specific towns or cities, and clusters were seen within families.
The first person to develop the condition in each of these families
was followed by a relative within several weeks. Many outbreaks were
centered around hospitals, places notorious for spreading disease.
The annual peak of new patients occurred in late summer, hinting at
possible spread of the disease through insects. Those scientists who
first thought the disease might be related to some noncontagious
occupational hazard were quickly dissuaded once the data showed that
the disease lacked the expected preferences. Farmers, for example,
who would be more easily exposed to pesticides, had a
lower-than-average incidence. Medical workers, on the other hand,
had a rather high rate of this condition - further suggesting it was
contagious.
However, the scientists investigating the epidemic did notice
some important contradictions. For instance, the disease had an odd,
amazingly consistent bias for striking middle-aged women, but was
less common among men and could hardly be found among children, who
normally transmit virtually any infectious disease. Careful medical
inspection showed that the symptoms did not coincide with those
typically expected for an infection. Blood and other bodily fluids,
which usually circulate a virus throughout the body, showed no
abnormalities, nor did the patients manifest any fevers, rashes, or
other signs of fighting off some invading germ. These important
pieces of evidence should have raised doubts about the viral
hypothesis.
The virus hunt pressed onward. Scientists were expecting to find
a virus that primarily induced diarrhea, as was the case in polio.
Looking back on this period, Kono has since become admirably frank
about his early biases, shared at the time by his fellow
virologists: "I was at that time engaged in poliovirus research, so
I suspected such a virus to be the cause."(1) Despite years spent
searching for the elusive virus, he never could isolate a single one
from any patient. Kono patiently reported his null results as he
plodded forward.
Meanwhile the epidemic was growing and the 1964 Olympic Games
were approaching. Ninety-six new cases had been diagnosed the
previous year, and the increased number of cases was being
accompanied by new symptoms. Some victims, for example, were now
suffering debilitating blindness. Preparing to host tourists from
around the world for the 1964 Olympics, Japan could ill afford to
have an uncontrolled plague. To make matters worse, forty-six new
patients suddenly appeared around the city of Toda, one of the
locations for Olympic events. Embarrassingly dubbed the "Toda
disease," this outbreak directly threatened Japan's reputation and
tourist industry while focusing public fear on the epidemic. Etsuro
Totsuka, later to become a lawyer for victims of the disease,
summarized the public mood at the time: "Even I was quite worried at
the time, as a university student studying physics. The general
public, including me, was extremely worried; we didn't know how to
prevent it, and there was no cure."(2)
In May of 1964, at the 61st General Meeting of the Japanese
Society of Internal Medicine, the disease was raised as a formal
topic. Kenzo Kusui, one of the first doctors to report patients
stricken with this condition, chaired that session. The
participating researchers gave the disease a formal name,
Subacute Myelo-Optico-Neuropathy (SMON), and they agreed on a
standardized clinical diagnosis. The Japanese Ministry of Health and
Welfare quickly provided a research grant and launched a formal
commission to investigate the epidemic under the leadership of
Magojiro Maekawa, a medical professor at Kyoto University. Kono was
one of several virologists named to the commission, thereby
establishing its mandate as a formal search for a virus.
The same year brought the first sign of a possible breakthrough.
Masahisa Shingu, a virologist at Kurume University and a fellow
member of the commission, announced his discovery of a virus in
excretions from SMON patients. The virus was classified as an
echovirus - an acronym for enteric cytopathogenic human orphan
virus. The viruses were called orphans because they had been
discovered accidentally during polio research but caused no disease.
Echoviruses were known for infecting the stomach or intestines, and
Shingu found evidence of infection in various SMON sufferers. He
excitedly drew the conclusion that this orphan virus had finally
been matched with a disease. Perhaps, he speculated, this virus
could also occasionally break into the nervous system, much like
poliovirus. He published the finding in 1965, unabashedly boasting
he had isolated the syndrome's cause.
But Kono, knowing the potentially disastrous results of blaming
the wrong microbe for the disease, took a more cautious attitude. In
1967, after three years of research trying to confirm Shingu's
claims, Kono could only report to a SMON symposium that he had not
isolated the virus from patients, nor could he find even indirect
evidence that the patients had previously been infected. Kono's
better judgment saved Japanese science from stampeding in the wrong
direction. He was fully vindicated four years later when other
researchers announced the same lack of evidence to suggest any
danger from Shingu's virus.
In the midst of this fruitless investigation, the Maekawa team
made a surprising observation that was tragically brushed aside.
According to surveys of hospitals, about half the SMON patients had
previously been prescribed a diarrhea-fighting drug known by the
brand name Entero-vioform, and the other half had received a
compound marketed under the name Emaform. Both drugs were prescribed
for problems of the digestive tract - the early symptom of SMON. The
suspicion naturally arose that these drugs might play some role in
the syndrome, but the commission, intent on the viral hypothesis,
bowed to the consensus view of SMON as contagious and quickly
dismissed this, noting that two different drugs should not cause the
same new disease. Had the commission researchers checked further,
however, they would have discovered that the two drugs were merely
different brand names applied to the same drug, a fact that did not
surface for several years.
The SMON commission dissolved in 1967, a failure. The cumulative
total of reported SMON cases had meanwhile reached nearly two
thousand by the end of 1966, a significant but not terrifying
number. If not for the quiet growth of the disease epidemic, the
floundering virus hunt might have killed public interest in SMON
research altogether.
Almost immediately after the official commission was dissolved,
two rural areas in the Okayama province began reeling from a new
explosive outbreak of the syndrome. Dozens of elderly women, and
some men in their thirties, began filling the nearby hospitals,
totaling almost 3 percent of the local population by 197I.
Scientific attention was again focused on SMON, with the specter of
a resurgent epidemic recharging the virus hunt.
Two researchers issued reports in 1968 describing a new virus
found in tissues of SMON patients, stirring a wave of excitement.
The agent fell under the classification of "Coxsackie" viruses, a
type of passenger virus known to infect the digestive tract and
originally discovered as a by-product of polio research. It was
another false alarm: The virus proved to be an accidental laboratory
contamination.
In 1969 the Japanese Ministry of Health and Welfare, anxious
about the expanding epidemic, again decided to form an official
investigating body. With more than ten times the funding of the old
1964 commission, the SMON Research Commission became the largest
Japanese research program ever devoted to a single disease. Its
first meeting was held in the heavily affected Okayama province in
early September. The consensus view among Japanese scientists had
completely focused on some unknown virus as the probable cause of
the disease. The naming of Kono, Japan's most respected virologist,
as chairman symbolically established the new commission's
priorities.
So far, after more than a decade of persistent research, the
virologists had come up painfully empty-handed. Kono, though himself
a virologist, now saw the need to explore alternative hypotheses.
Kono divided the commission's work into four sections, each led by
top Japanese medical officials. An epidemiologist was put in charge
of a group conducting nationwide surveys on the extent,
distribution, and associated risk factors of the disease. Kono
himself headed the virology group. A pathologist headed a group
focused on analyzing autopsy results, and a neurologist led a group
classifying neurological and intestinal SMON symptoms. Altogether,
forty top scientists participated in the commission during 1969.
Although Kono had opened the door for alternative research
directions, the virus hunt accelerated - for just at this time, some
key scientific claims by English and American virologists were
beginning to have a profound impact on virus research worldwide, and
particularly on SMON research in Japan. The first came in the early
1960s from virologist Carleton Gajdusek of the American National
Institutes of Health, who reported finding evidence of the first
"slow virus" in humans. (A slow virus is a virus alleged to produce
a disease long after the original infection, that is, after a long
"latent period.") He believed it to be the cause of kuru disease
among New Guinea natives. Kuru was a slowly progressing neurological
disease that led to the debilitation of motor skills. The patients
presented with symptoms of tremor and paralysis similar to
Parkinson's disease. Gajdusek claimed to have found the kuru virus,
but his methods were highly unusual by any scientific standards. He
had never actually isolated a virus but instead had ground up the
diseased brains of dead kuru victims and injected these unpurified
mixtures into the brains of living monkeys. When some of the monkeys
showed deficits in motor skills, Gajdusek published his findings in
the world's oldest scientific journal, Nature, and was lauded by his
fellow virologists. The second alleged discovery came from London's
Middlesex Hospital in 1964, directly inspired by Gajdusek's claims.
Two researchers found a virus that was believed to cause the
childhood cancer, Burkitt's lymphoma. It was the first virus ever
claimed to cause human cancer and the first known human virus
thought to have an incubation time between infection and disease
measured in years, rather than days or weeks.
These claims were made by very large and respected research
establishments; therefore, Kono could not afford to ignore them.
Other medical experts on the SMON commission warned him that the
SMON symptoms did not resemble those of standard virus infections,
suggesting the condition was not contagious. Kono, however, brushed
aside this advice, arguing that if scientists were unwilling to
consider the possible existence of nonclassic viruses then "Dr.
Gajdusek could not have established a slow virus etiology for
kuru."(3) Imitating Gajdusek's methods, he injected unpurified
fluids from SMON patients into the brains of experimental mice and
monkeys, hoping to cause the disease and isolate the guilty virus.
Frustrated, but not willing to give up, he decided the American
researchers were better equipped to find such a virus. He mailed the
same fluid samples directly to Gajdusek, who repeated the
inoculations into the brains of his own chimpanzees; after three
years, they, too, remained perfectly normal. With that, Kono finally
abandoned the search for a "slow virus."
With their virus research faltering, a few of the investigators
began looking for bacteria. One lab found that SMON patients had
imbalanced levels of the beneficial bacteria normally growing in
everyone's intestines, but it could not isolate any new invading
microbe. Kono's own lab, as well as two other researchers, did
notice unusually large amounts of a mycoplasma, one type of
bacterial parasite, in disease victims. However, since mycoplasma
are found in a large percentage of human populations and are usually
known for being either relatively harmless or causing some
pneumonias, Kono and his fellow researchers decided against pursuing
this further.
By 1970, one fact stood out more agonizingly than any other:
Twelve years of microbe research into the SMON epidemic had yielded
nothing but dead ends. Yet the pressure continued to mount as the
death toll rose. The year 1969 alone claimed almost two thousand new
SMON victims, the worst toll ever. Kono and his commission were
running out of options.
Fortunately for the Japanese people, several researchers on the
commission were not virus hunters, and these scientists actually
rediscovered the evidence for a toxin-SMON hypothesis.
The Drug Connection
As the race to find a SMON virus was capturing all the attention,
other scientists were turning up some important clues to the
mysterious syndrome. One pharmacologist, Dr. H. Beppu, visited the
hard-hit Okayama province in 1969 to investigate the increasing
outbreak and independently discovered the same coincidence the
Mackawa group had years earlier - that SMON victims had taken
certain drugs to treat diarrhea. Unlike the Maekawa group, Beppu
investigated and found that Entero-vioform and Emaform - the
diarrhea-fighting drugs found present in an earlier SMON study -
turned out to be different brand names for a substance known as
clioquinol, a freely available medical drug used against some
types of diarrhea and dysentery. Beppu fed the chemical to
experimental mice, hoping to see nerve damage like that in SMON, but
was disappointed when the mice merely died. He missed the
significance of his own results. Clioquinol was sold because it was
believed not to be absorbed into the body, instead remaining in the
intestines to kill invading germs. The death of Beppu's animals,
however, proved that the drug not only entered the body, but could
kill many essential tissues in the animal. His experiment led the
SMON commission to rediscover this clioquinol connection the
following year. "He later confessed to feeling stupid, because he
gave up the experiment when the animals died," Totsuka explained of
Beppu. "He wanted to prove a neurological disorder, but only proved
the drug's severe toxicity."(4)
Meanwhile the SMON commission's first priority lay in conducting
a nationwide survey of SMON cases reported since 1967, gathered by
sending questionnaires to doctors and hospitals throughout Japan. In
the fall of 1969, shortly after the commission began analyzing
survey data, the head of the clinical symptoms section came across
several SMON patients with a strange green coating on their tongues,
a symptom unnoticed before nationwide data were gathered. At first
other researchers on the commission suggested that this new symptom
might be caused by Pseudomonas bacteria, which can release
colorful blue and green pigments. One of the investigators did
isolate such a bacterium from some patients but not from others, and
the inexplicable symptom merely became a part of the revised SMON
definition. The green tongue observation achieved new importance in
May of 1970, when one group of doctors encountered two SMON patients
with greenish urine. Enough of the pigment could be extracted to
perform chemical tests. Within a short time the substance was
determined to be an altered form of clioquinol, the same drug
previously found by the Maekawa commission and by Beppu.
This raised two very troubling questions. Clioquinol had been
marketed for years on the assumptions that it only killed amoeba in
the intestinal tract and could not be absorbed into the body; its
appearance on the tongue and in the urine now proved this belief
wrong. Could the medicine therefore have unexpected side effects?
And why would SMON patients manifest the drug by-products so much
more obviously than the rest of the population? This latter question
particularly bothered one neurology professor at Niigata University,
Tadao Tsubaki. Making an educated guess, he openly formulated the
hypothesis abandoned by earlier investigators - that SMON might be
the result of clioquinol consumption, not of a virus.
As expected, the interpretation of SMON as a noncontagious
syndrome did not become popular among the virus hunters. And the
suggestion that clioquinol might be guilty met even stronger
resistance, for the drug was being used to treat the very abdominal
symptoms found in SMON. Doctors, naturally, were reluctant to
believe they were exacerbating these abdominal pains and thus adding
the severe insult of nerve damage to the injury. Totsuka recalled
that "doctors and scientists wanted to believe in a virus, because
they prescribed clioquinol. One of the drug's main side effects was
constipation and abdominal pain. Now because the drug caused pain,
doctors again prescribed the drug."(5) Doctors, ignorant of
clioquinol's side effects, assumed the stomach pains resulted from
the primary sickness and kept increasing the dose in a vicious
cycle.
Tsubaki knew he had to gather strong evidence before they could
shoot down the virus-SMON hypothesis. Pulling together several
associates, Tsubaki arranged for a small study of SMON patients at
seven hospitals. By July of 1970 he had already compiled enough data
to draw several important conclusions: 96 percent of SMON victims
had definitely taken clioquinol before the disease appeared, and
those with the most severe symptoms had taken the highest doses of
the medication. The number of SMON cases throughout Japan, moreover,
had risen and fallen with the sales of clioquinol.
This clioquinol hypothesis explained all the strangest features
of the SMON syndrome, such as its preference for striking middleaged
women, its absence in children (who received fewer and smaller doses
of the drug), and its symptomatic differences from typical viral
infections. It also shed new light on the supposed evidence that
SMON was infectious: its tendency to appear in hospital patients, to
cluster in families, to afflict medical workers, and to break out
more heavily in the summer - all of these reflected the patterns of
clioquinol use. The epidemic itself had begun shortly after approval
for pharmaceutical companies to begin manufacturing the drug in
Japan.
In 1970 there were thirty-seven SMON cases in January and nearly
sixty more cases during the month of July. The Japanese Ministry of
Health and Welfare decided not to wait any longer, and promptly
released the information about clioquinol to the press. The news of
Tsubaki's research reached the public in early August, and the
number of new SMON cases for that month dropped to under fifty,
presumably because some doctors stopped prescribing clioquinol to
their patients. On September 8 the Japanese government banned all
sales of the drug, and the total new caseload for that month sank
below twenty. The following year, 1971, saw only thirty-six cases.
Three more cases were reported in 1972, and one in 1973. The
epidemic was over.
For the next few years, the commission's research focused on
confirming the role of clioquinol. In 1975 it released a
comprehensive report. Systematic epidemiological surveys matched use
of the drug with outbreaks of the syndrome, and experiments were
performed on animals ranging from mice to chimpanzees. As it turned
out, the drug induced SMON-like symptoms most perfectly in dogs and
cats. Meanwhile, the investigators began uncovering individual case
reports of SMON symptoms from around the world, wherever clioquinol
had been marketed. Totaling roughly one hundred cases, the published
reports ranged from Argentina in the 1930S to Great Britain, Sweden,
and Australia in more recent times, often with the doctor
specifically pointing out the association with the use of clioquinol
or similar compounds. Ciba-Geigy, the international producer of the
drug, had received warnings of these incidents years before the
Japanese epidemic, a fact that later became the basis of a
successful lawsuit against the pharmaceutical company.
Clioquinol, often marketed under the brand name Enterovioform,
has been available for decades throughout many countries in the
world. But while doctors outside Japan have published a few reports
of SMON-like conditions, no real epidemic of the disease has ever
broken out in Europe, India, or other countries with widespread use
of the drug. Much of the difference lies in the heavier consumption
of clioquinol in Japan, where the stomach, rather than the heart, is
considered the seat of the emotions. The general over-prescription
of drugs in that country further worsens the problem, such that many
SMON victims had histories of using not only clioquinol but also
multiple other medications, often at the same time. Government
health insurance policies have encouraged this over-medication,
paying doctors for every drug prescribed to the patient. As a
result, the proportion of the Japanese health insurance budget spent
on pharmaceutical drugs grew from 26 percent in 1961 to 40 percent
in 1971, a level many times higher than in other nations. By the
time the Japanese government decided to ban clioquinol, many of the
hardest-hit SMON patients had each consumed hundreds of grams over
the course of several months. And whereas the outside world mostly
used clioquinol to prevent diarrhea when traveling abroad, the
Japanese usually received the drug as hospital patients, having an
already weakened condition.
Years later, at a 1979 conference, Reisaku Kono asked, "Why had
research on the etiology of SMON not hit upon clioquinol until
1970?" The question has two answers; both pointed out by Kono
himself:
There were at least two occasions when physicians suspected
that clioquinol might have something to do with SMON. I know of
a certain professor rebuking one of his staff physicians for
connecting clioquinol with SMON. In 1967 the study group of the
National Hospitals on SMON reported as follows: Entero-vioform
(clioquinol's brand name), mesaphylin, Emaform (home producer of
clioquinol), chloromycetin and llosone were often prescribed to
SMON patients, but no link was found between Entero-vioform and
SMON. This report referred to Entero-vioform in particular so
that clioquinol must have been suspected by someone in the study
group. Dr. Tsugane, who was responsible for the survey, said
that the survey was not thorough enough to unearth clioquinol as
a causative agent. One of the reasons could have been that
clioquinol had been used as a drug for the intestinal disorders
of SMON, and it was hard to believe that clioquinol was toxic
rather than a remedy. (6)
Referring here to the tentative fingering of clioquinol by the
Maekawa group, Kono observed that too many medical doctors refused
to recognize the possibility of an iatrogenic disease (one caused by
the doctor's treatment). They understandably disliked the idea that
a drug might cause some of the very symptoms for which it was
prescribed in the first place.
Another, more fundamental, reason for overlooking clioquinol lay
in the prevailing attitude of the virologists. As expressed by Kono,
"We were still within grasp of the ghosts of Pasteur and Koch!"(7)
SMON, a vaguely polio-like syndrome, had first appeared in the midst
of a war against polio. The polio virologists, Kono included, were
naturally inclined to search for a new virus as the cause of the new
disease. The Japanese government, having funded poliovirus research,
simply kept up the momentum by funding the same virologists to study
SMON. Thus, the virus hunters received the lion's share of research
moneys and attention, and with that the power to direct the SMON
research program. Had it not been for Kono's foresight in also
appointing nonvirologists to the commission, the epidemic might have
lasted much longer.
At least the epidemic had ended, with the truth universally
recognized. The virologists had learned their lesson, and the search
for SMON viruses was over.
Or was it? Incredibly, against all evidence, the SMON virus hunt
suddenly came back to life within weeks of the epidemic's end. The
fight over the cause of the syndrome was to drag on for several more
years, with the virus hunters simply ignoring the fact that SMON
itself had disappeared after the ban on clioquinol.
The Virus Hunt Revived
In February of 1970, while the SMON Research Commission was still
scrambling to find the cause of the epidemic and a few researchers
were just beginning to notice the greenish pigments in some
patients, Assistant Professor Shigeyuki Inoue at Kyoto University's
Institute for Virus Research claimed discovery of a virus in the
spinal fluid and excretions of SMON patients. He added the extracts
to laboratory culture dishes of hamster tumor cells and found that
the new agent killed the cells. With more experimentation, Inoue
classified the microbe as a new herpes virus. He was able to isolate
this particular virus from nearly all SMON patients he tested, more
than forty in all, and found antibodies against the virus in other
victims.
Reisaku Kono moved promptly to test these new observations. He
used Inoue's own virus isolate and cell cultures, and within three
months of Inoue's first report found that the virus could kill some
cells. These particular cells, however, were extremely sensitive,
prone to spontaneous death even in the uninfected cultures. Kono
began to suspect the virus was harmless. He also could not isolate
the virus from any SMON patients, unlike Inoue's lab. Perhaps, he
openly wondered, the alleged virus might not exist at all.
A number of scientists sided with Kono, insisting they could
neither find the virus in SMON victims nor cause cell death in
culture dishes by adding virus samples from Inoue's lab. Nor could
Inoue's extracts induce symptoms when injected into mice. Indeed,
Kono and some of these other investigators could never even find the
virus at all, reinforcing the growing question of whether it truly
existed. The virus could not even be detected in the samples sent
them from Inoue. An occasional mouse injected with Inoue's supposed
virus would become sick, but the symptoms did not resemble those of
SMON. Kono won allies among his peers when many of them could not
reproduce Inoue's observations. a troubling problem for any
scientific claim.
Nevertheless, Inoue had meanwhile rapidly achieved celebrity
status for his "SMON virus" during 1970, before the clioquinol
announcement that August. The Japanese news media had prematurely
publicized his results, creating the widespread impression that the
cause of SMON had been determined. Hysteria over the contagious
plague swept through much of the country, causing frightened family
members of SMON patients to avoid contact with their "infected"
relatives, and leading many of the victims to commit suicide.
"Patients were isolated, many committed suicide, and there was
national panic," reflected Totsuka on the horror he witnessed. "I
met families who lost relatives. I heard from most or all of my goo
clients; most of the patients said they very much feared and dreaded
the disease. Everybody told me about that, about those sufferings.
Once they found out about the drug, they were somewhat relieved,
because it was not infectious."(8)
The new virus-SMON hypothesis had indeed achieved a life of its
own, causing a few scientists to Jump on the Inoue bandwagon; months
after clioquinol had been banned and the epidemic had
virtually disappeared, several labs excitedly issued reports
claiming they could reproduce Inoue's findings. Inoue himself
further insisted he had caused SMON-like symptoms in mice -
including weight loss, paralysis, and nerve damage - either by
injecting the virus into their brains or feeding the virus to other
immune-suppressed mice unable to fight off the infection. Inoue and
a collaborating scientist also both claimed to have photographed the
virus directly with electron microscopes, although Inoue's colleague
eventually retracted his own report as having been mistaken.
A meeting of the SMON Research Commission was finally held in
July of 1972 to resolve the controversy. Until that time, Inoue's
results had received attention and concern equal to the clioquinol
research. But based on the inability of many scientists to produce
the same results, which must be done for any scientific hypothesis
to be accepted, the members at the meeting decided not to focus any
more research efforts on the Inoue virus. Samples were frozen for
future study, and the group thereafter devoted its resources to
studying clioquinol.
Despite the absence of confirming evidence, and despite the
disappearance of SMON following the ban on clioquinol, Inoue and his
supporting colleagues continued to publish reports of evidence for
the virus hypothesis. This publicity carried the Inoue hypothesis
overseas, leading the 1974 edition of the Review of Medical
Microbiology, an American textbook, to incorporate the Inoue
virus hypothesis of SMON.
Shocked and angered by the favorable publicity surrounding
Inoue's hypothesis, Kono wrote a letter to the British medical
journal Lancet; the letter was published in August of 1975.
The international popularity of virus research had whetted
scientists' appetite for Inoue's hypothesis, but Kono also knew he
was battling a nearly complete ignorance of the SMON episode outside
Japan:
Inoue et al. published several papers on SMON virus, and a
standard textbook adopted Inoue's virus theory as confirmed.
However, research in the laboratories of the SMON Research
Commission in Japan failed to confirm Inoue's results.
Unfortunately, this negative information has not been published
in English.(9)
The epidemic's toll had officially ended in 1973 with 11,007
victims, including thousands of fatalities. Angered upon learning of
Ciba-Geigy's disregard of previously reported clioquinol toxicity,
many of these patients filed a lawsuit in May of 197I against the
Japanese government, Ciba-Geigy of Japan, fifteen other distributors
of the drug, and twenty-three doctors and hospitals. The ranks of
the plaintiffs soon swelled to some forty-five hundred, with legal
action initiated in twenty-three Japanese district courts. The
largest group of SMON victims sued jointly in the Tokyo District
Court. When frustrations mounted over the slow and indecisive
actions of their lawyers, nine hundred of the plaintiffs broke away
to form a second group. The aggressive investigations conducted by
this new legal team reinvigorated the case, bolstering the positions
of the plaintiffs in parallel lawsuits. Etsuro Totsuka, one of the
thirty members of this legal team, has described the fight:
We were the only team gathering information outside Japan,
inviting foreign experts to testify in Japanese courts,
discovering the United States FDA had restricted clioquinol ten
years before Japan, and waging an international campaign against
Ciba-Geigy...
We found many foreign doctors who had reported clioquinol
side effects before. They were contacted by Ciba-Geigy, and
except in one or two instances were persuaded not to help us. By
the time I saw the doctors, they had already been contacted by
the other side. They had been invited on trips, some to
Ciba-Geigy's headquarters... We felt they were already
compensated, under the condition not to tell us anything.(10)
The two sides slugged it out for several years, but the testimony
by members of Kono's SMON Research Commission proved devastating,
and a string of legal victories followed in the courts.
Today most scientists and laymen outside Japan have never heard
of the virus-SMON controversy, even in the face of the lawsuit
against the distributors of clioquinol, television documentaries in
Germany and England on clioquinol, and two conferences during the
1970s on iatrogenic (medically caused) disease. The story that SMON
research had ignored the evidence of a toxic cause for fifteen years
and had sacrificed thousands of human lives to a flawed virus
hypothesis is too embarrassing to the virus-hunting establishment to
record. *
The above article has been extracted from: Peter H. Duesberg,
'Inventing the AIDS Virus' Regnery USA 1996, 720 pages, ISBN
0-89526-470-6.
References:
1. R. Kono, "The SMON Virus Theory," Lancet, ii
(1975): 370-371; I. Shigematsu, H. Yanagawa, S.I. Yamamoto, and K.
Nake, "Epidemiological Approach to SMON (Subacute
Myelo-Optico-Neuropathy)," Japanese Journal of Medicine, Science,
and Biology, 28 Supplement (1975): 23-33
2. E. Totsuka, personal communication, 1
May 1992.
3. T. E. Soda, Drug-lnduced Sufferings: Medical,
Pharmaceutical, and Legal Aspects (Amsterdam: Excerpta Medica,
1980).
4. Totsuka, personal communication, 1 May
1992.
5. Ibid.
6. Soda, Drug-lnduced Sufferings.
7. Ibid.
8. Totsuka, personal communication, 1 May
1992.
9. Kono, "SMON Virus Theory," 370-371.
10. Totsuka, personal communication, 1 May
1992.
11. Soda, Drug-lnduced Sufferings.