Failed Hypotheses

Original Publication
HEAL Toronto

How popular consensus and the medical establishment have often stubbornly clung to the wrong ideas.

Any medical dictionary will tell you that influenza is caused by a virus or that scurvy results from lack of vitamin C - both pieces of common knowledge. Less well known is the fact that the majority of doctors and scientists started out with the wrong ideas about these and many other diseases. It is often the case that what becomes common knowledge has first to be argued by a lone dissenting voice against huge resistance. Science is regularly reminded that Nature is oblivious to democracy. Derek Freeman, who challenged Margaret Mead on Coming of Age in Samoa, once said, " To seek to dispose of a major scientific issue by a show of hands is a striking demonstration of the way in which belief can come to dominate the thinking of scholars." The prevailing hypothesis, in the long run, is a matter of natural selection - not popular opinion.

History recalls many disease conditions that led people to wrongly believe that an infectious agent was to blame. Often this is assumed when clusters of people fall ill in a short period of time. Scurvy was originally thought to be an infectious disease because sailors on long voyages tended to come down with it en masse. By the early 1600s some English naval officers were recognizing that citrus juice could prevent and cure scurvy. Reports to the Admiralty fell on deaf ears. When Dr. James Lind, a British naval surgeon, published a book in 1753 establishing that scurvy was in fact brought about by a nutritional deficiency it took 40 years for his discovery to be accepted by the prevailing medical orthodoxy of the day. Finally, the British navy changed its tack and provided sailors with scurvy prophylaxis in the form of lime and lemon juice -- thus giving rise to the nickname "limeys."

Pellagra was a low-level problem throughout the Southern USA for years, but by the 1900s crop failures and an economic downturn had raised it to epidemic proportions. Joseph Goldberger offered conclusive evidence that poor nutrition was the culprit in causing pellagra. Goldberger had trouble convincing others of what he had found. He spent the rest of his life looking for what exactly was missing in the diet that caused pellagra, but this would not be uncovered until after his death. He also was thwarted by the medical world's obsession with infectious disease, newly understood and in some cases treatable, and the political world's resistance to hearing that poor social conditions could cause disease. His ideas received the same offhand dismissal that AIDS dissidents now encounter.

Nutritional sciences were in their infancy at the start of the 20th century. Unknown was the concept that minerals and vitamins were necessary to prevent diseases caused by dietary deficiencies. Recurring nutritional deficiency diseases, including rickets, scurvy, beri-beri, and pellagra were thought to be infectious diseases. By 1900, biochemists and physiologists had identified protein, fat, and carbohydrates as the basic nutrients in food. By 1916, new data had led to the discovery that food contained vitamins, and the lack of "vital amines" could cause disease. These scientific discoveries and the resulting public health policies, such as food fortification programs, led to substantial reductions in nutritional deficiency diseases during the first half of the century. [MMWR 48(40);905-913]

Iatrogenic diseases, caused by medical treatment, can sometimes be the consequence the wrong ideas about the causes of illness. In the 19th century, puerperal or "childbed" fever was blamed variously on overcrowding, poor ventilation, the onset of lactation, or miasma. Semmelweis investigated and concluded that medical students who came directly from the dissecting room to the maternity ward carried the infection from mothers who had died of the disease to healthy mothers. (Doctors at that time were not in the practice of washing their hands.) His discovery, for a long time ignored, eventually lead to antisepsis in medical practice. One of the worst iatrogenic epidemics happened in Japan. The disease, called SMON, was blamed for over ten years on various viruses, until it was discovered that the drug used to fight the disease - Clioquinol (marketed by Ciba-Geigy under the name Entero-Vioform) - was actually its cause. By the time the government finally banned the drug in 1970, 11,000 people had been afflicted by SMON in Japan. Iatrogenic disease due to pharmaceutical drugs may be a far greater problem than we realize. One indication is the fact that 100,000 Americans die each year from adverse reactions to prescription drugs -- the USA's fourth-leading cause of death -- and that is just among hospital patients (JAMA 1998; 279: 1200-05). Estimates suggest that pharmaceuticals are responsible for 199,000 additional deaths among out patients (BMJ 2000;320:774-777).

• Disease is considered to be a harmful deviation from the normal structural or functional state of an organism. A diseased organism commonly exhibits signs or symptoms indicative of its abnormal state. Thus, the normal condition of an organism must be understood in order to recognize the hallmarks of disease. Nevertheless, a sharp demarcation between disease and health is not always apparent. -- [Encyclopedia Britannica 1996]

Scurvy

Hippocrates described Scurvy: bleeding gums, hemorrhaging and death, as early as the 5th c. BC. During the Crusades the disease became widespread. In 1250 it forced the retreat and capture of St. Louis with all his knights. It didn't become a major problem, however, until the age of exploration. Long sea voyages lacking in fresh food led to vitamin C deficiency.

There is a legend that during one of Christopher Columbus's voyages some Portuguese sailors had scurvy and wanted to be dropped off at one of the nearby islands and die there rather then dying on board and being fed to the fish. While the men were on the island they ate some of the island's fresh fruits and plants and to their amazement began to recover. When Columbus's ships passed by several months later, the pilot was surprised to see the men waving from land alive and healthy. The island was named Curacao, meaning Cure.

During Jacques Cartier's second voyage (1535-36), he used two indian interpreter-guides to pilot him up the St. Lawrence River to Stadacona (the site of modern Quebec). Wintering in Stadacona, 25 members of his crew died from scurvy before the indians taught them to drink a brew of white cedar which saved the rest.

As early as 1593, during a voyage to the South Pacific, Sir Richard Hawkins recommended the following treatment for scurvy: "That which I have seen most fruitfull for this sicknesse, is sower [sour] oranges and lemmons." In 1601 Captain James Lancaster unintentionally performed a controlled study of lemon juice as a preventive for scurvy. His fleet of four ships departed an April 21, 1601, and scurvy began to appear in three of the ships by August 1 (4 months after sailing). By the time of arrival, September 9, the three ships were so devastated by scurvy that the men of Lancaster's ship had to assist the rest of the fleet into the harbor. Lancaster's men remained in better health than the men on the other ships because he brought to sea bottles of lemon juice, which he gave to each one as long as it would last, three spoonfuls every morning. The Admiralty received Lancaster's report.

John Woodall, the 'father of naval hygiene', a "Master in Chirurgerie" published "The Surgeon's Mate" in 1636. He unequivocally wrote that scurvy could be prevented by the use of fresh vegetables and the use of lemons and oranges. "The juyce of lemmons is a precious medicine and well tried; being sound and good. Let it have the chief place for it will deserve it. The use whereof is: It is to be taken each morning two or three teaspoonfuls, and fast after it two hours., Some chirurgeons also give of the juyce daily to the men in health as preservative."

Woodall's book was published 111 years before Lind's famous experiment on the Salisbury in 1747 and 159 years before the British Navy finally mandated lemon juice for all sailors in 1795. "It is estimated that 5000 lives a year were needlessly lost from scurvy during this period: that is a total of nearly 800,000. In the 200 years from 1600 to 1800 nearly 1,000,000 men died of an easily preventable disease. There are in the whole of human history few more notable examples of official indifference and stupidity producing such disastrous consequence to human life." (Louis H. Roddis, A Short History of Nautical Medicine)

from: A Short History of Scury by Mark R. Anderson, M.D.

Puerperal or "Childbed" Fever

An infection, once prevalent in women after childbirth, most cases of puerperal fever occurred because aseptic techniques during delivery and occasionally during abortion and miscarriage were not used. Also called childbed fever, the infection in most instances was due to streptococci that entered the body during delivery. The efforts of the physicians Ignaz Philipp Semmelweis and Oliver Wendell Holmes brought about the adoption of rigid cleanliness and asepsis in maternal delivery procedures, and the mortality from puerperal fever was reduced more than 90 percent after their adoption. In addition to the use of strict asepsis in obstetrical procedures, the availability of modern antiseptics has made puerperal fever a rarity.

Ignaz Philipp Semmelweis (1818-65), a Hungarian obstetrician, who discovered how to prevent puerperal fever from being transmitted to mothers, introduced antisepsis into medical practice. Semmelweis received his doctor's degree from Vienna in 1844 and was appointed assistant at the obstetric clinic in Vienna. He soon became involved in the problem of puerperal infection, the scourge of maternity hospitals throughout Europe. Although most women delivered at home, those who had to seek hospitalization because of poverty, illegitimacy, or obstetrical complications faced mortality rates ranging as high as 25-30 percent. Some thought that the infection was induced by overcrowding, poor ventilation, the onset of lactation, or miasma. Semmelweis proceeded to investigate its cause over the strong objections of his chief, who, like other continental physicians, had reconciled himself to the idea that the disease was unpreventable.

Semmelweis observed that, among women in the first division of the clinic, the death rate from childbed fever was two or three times as high as among those in the second division, although the two divisions were identical with the exception that students were taught in the first and midwives in the second. He put forward the thesis that perhaps the students carried something to the patients they examined during labour. He concluded that students who came directly from the dissecting room to the maternity ward carried the infection from mothers who had died of the disease to healthy mothers. He ordered the students to wash their hands in a solution of chlorinated lime before each examination. Under these procedures, the mortality rates in the first division dropped from 18.27 to 1.27 percent, and in March and August of 1848 no woman died in childbirth in his division.

Semmelweis nevertheless encountered strong opposition from hospital officials, and because of his political activity as well, left Vienna in 1850 for the University of Pest, where he became professor of obstetrics at the university hospital. In spite of his enforcing antiseptic practices and reducing the mortality rate from puerperal fever to 0.85 percent, Semmelweis's findings and publications were resisted by hospital and medical authorities in Hungary and abroad.

Source: Encyclopædia Britannica, Inc.

Pellagra shown to be dietary disease

Joseph Goldberger (1874 - 1929) was born in the Austria-Hungary, in a town now located in the Czech Republic. In 1881, when he was six, his family emigrated to the United States. At age 16, he entered City College in New York, intent on studying engineering. After dropping in one day on a lecture at Bellevue Hospital Medical College, he changed his mind. He obtained a medical degree from Bellevue in 1895. He had a private practice in a small city in Pennsylvania, but after two years realized he was bored. He took the competitive exam to enter the Marine Hospital Service, and in 1899 joined its ranks.

The Marine Hospital Service was established by Congress in 1798 to care for merchant seamen who were sick, and its main goal was fighting epidemics. By the end of the nineteenth century, in the wake of medical discoveries about germs, the Service's officers considered themselves "microbe hunters." In 1902 the Marine Hospital Service was renamed the Public Health Service, and over the decades, it turned more and more to basic science. In 1912, Congress re-formed the Service, expanding its duties to include investigating human diseases.

Goldberger had been fighting tropical fevers, typhus, typhoid, and other infectious outbreaks throughout the United States and the Caribbean. The Surgeon General took note of his energy and success and in 1914, appointed him to tackle the crisis of pellagra. Pellagra had been a low-level problem throughout the South for years, but crop failures and an economic downturn had raised it to epidemic proportions. The disease causes skin rashes, mouth sores, diarrhea, and if untreated, mental deterioration. Goldberger's first step was to simply observe. He traveled tirelessly through the South, taking notes, asking questions, and watching. He noticed that the diet of poor people in the region consisted of cornbread, molasses, and a little pork fat. It seemed that the poorer people were, the more likely they were to get pellagra. Institutions such as prisons, asylums, and orphanages also had a limited diet and a great deal of pellagra -- among inmates. Goldberger gradually concluded that the disease was not infectious at all, but strictly a matter of diet.

In 1915, he conducted experiments on inmates at a Mississippi prison, who volunteered for the study in exchange for a pardon. Because it was a farm prison, its inmates had a fairly balanced diet. Goldberger's volunteers were given the poor Southern diet he had seen associated with pellagra. That was the only difference. The other inmates ate the usual farm fare. Every effort was made to prevent and rule out infectious transmission. And within months, the volunteers came down with pellagra. Then the researchers tried to catch the disease from those already suffering -- they couldn't. The pellagra symptoms disappeared when the volunteers were given meat, fresh vegetables, and milk.

Despite this conclusive evidence, Goldberger had trouble convincing others what he had found. He spent the rest of his life looking for what exactly was missing in the diet that caused pellagra, but this would not be uncovered until after his death. He also was thwarted by the medical world's obsession with infectious disease, newly understood and in some cases treatable, and the political world's resistance to hearing that poor social conditions could cause disease.

In 1937, researcher Conrad Elvehjem found that nicotinic acid, or niacin, prevented and cured pellagra in dogs. It works as well in humans. Niacin is one of the B vitamins. During the 1930s, great strides were made in understanding the way vitamins work in the chemistry of our bodies.

Source: PBS Online

The SMON tragedy

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.

Clioquinol, a Ciba-Geigy product, was considered to be perfectly safe, its effects confined to the digestive tract where it was supposed to destroy germs associated with diarrhea without being absorbed into the bloodstream. However, Dr Beppu demonstrated this belief to be untrue. When he fed the chemical to experimental mice they all died. He had hoped the mice would display the nerve damage associated with SMON, but when they did not do so he discontinued the experiment, not realizing the significance of their deaths.

The commission's survey revealed also that a number of SMON patients had displayed a strange green coating on their tongues, and other patients had passed greenish coloured urine. Chemical tests revealed the colouring agent to be an altered form of Clioquinol.

This evidence was enough for Professor Tadao Tsubaki, a neurologist at Niigata University, to state outright his belief that SMON was caused by Clioquinol and not by a virus. This viewpoint, which one would think would have been clear to everybody by now, was not readily accepted, particularly by doctors who habitually and routinely prescribed the drug.

But the evidence was irrefutable. The SMON epidemic had clearly commenced within a short time after the government's approval for pharmaceutical companies to manufacture Clioquinol in Japan, and it lasted until just after the government finally banned the drug in September 1970. Whereas 2,000 cases were reported in 1969, in 1971 the number of cases had fallen to only thirty-six, in 1972 to three and in 1973 to one.

Later investigation showed that Clioquinol caused symptoms of SMON in animals too, and that wherever in the world the drug had been used, individual cases of the condition in humans had earlier been reported as associated with the drug. Furthermore, Ciba-Geigy, the international producer of Clioquinol, had knowledge of these incidents but nevertheless continued selling the drug worldwide, a fact that later became the basis of major law suits against them. (The US Food and Drug Administration restricted the sale of Clioquinol ten years before it was banned in Japan.)

That no epidemic of SMON had occurred elsewhere is explained by several circumstances peculiar to Japan. In Japanese culture the seat of human emotions is regarded to be the stomach, rather than the heart, the Japanese people are very germ conscious; and lastly (but not least), overmedication is more common in Japan than elsewhere because doctors receive payment from the government health insurance for every drug they prescribe. Many SMON "victims" had histories of taking multiple medications, often together.

While it is easy to be wise after the event and criticize the Japanese medical establishment for its lamentable inertia in resolving the SMON problem, it can be seen that their performance was no worse than the past and ongoing performance of the establishment everywhere. The reason the highly qualified Japanese professors had not been able to discern what now appears obvious, was explained--at least in part--by Professor Kono who observed that many medical doctors simply refused to recognize that iatrogenic disease could occur. But a more fundamental reason, according to Professor Kono, was the beliefs indoctrinated into virologists generally. He added: "We were still within the grasp of the ghosts of Pasteur and Koch!"

Such is the futility--and danger--of the medical obsession with germs and viruses, and the chemical drugs with which doctors hope to destroy them. In the words of Professor Duesberg of the University of California:

"SMON and AIDS are intimately connected; they are only two episodes in a long series of disasters, all emanating from a single, ongoing, self propagating scientific program-virus hunting. This research effort, growing relentlessly, has for three decades been misleading science and the public about medical conditions ranging from cervical cancer to Chronic Fatigue Syndrome, from Alzheimer's Disease to Hepatitis C, and many more. All these smaller programs are failing in their public health goals as they prescribe the wrong treatments and preventive measures, while generating unnecessary fear among the lay public."

Source: HEALTH & SURVIVAL IN THE 21st CENTURY by Ross Horne

For a more indepth look at SMON:

The SMON Fiasco by Bryan Ellison & Peter Duesberg