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SammyJo wrote:Is there a scientific standard we can consult, like how much past corroboration needs to pile up before the scientific community can reach a conclusion?

THE BIOLOGICAL SIGNIFICANCE OF THE LESIONS OF MULTIPLE SCLEROSIS
Putnam
Science 28 September 1934: 295-296
DOI: 10.1126/science.80.2074.295

VASCULAR PATTERN OF LESIONS OF MULTIPLE SCLEROSIS

ROBERT S. DOW, M.D., Ph.D.; GEORGE BERGLUND, B.S.


Arch Neurol Psychiatry. 1942;47(1):1-18.

The theory of a relation between the cerebrovascular system and the lesions of multiple sclerosis has been advanced by many workers. The first of many to assign a primary role to vascular lesions was Rindfleisch.1 Ribbert2 early maintained that the demyelinated areas were related to a primary disseminated thrombosis. He described a congested central vessel in all the sclerotic patches. In two small patches cut in serial section he found white blood cells in the lumen of the vessel, partly adherent to the vessel wall and partly filling the vessel as an embolus. He stated that these changes in the vessel were multiple thrombi and expressed the belief that they had an important causative role in multiple sclerosis. The most recent adherents to the idea that vascular lesions play a primary role in the pathogenesis of the lesions of multiple sclerosis have been Putnam and his collaborators.3 . . .

ozarkcanoer wrote:My first response is if Putnam created an animal model that looked like MS then why wasn't there any follow up ?? The depression ? WWII ? Or just ignored like Gregor Mendel's genetics work.

RESULTS OF TREATMENT OF MULTIPLE SCLEROSIS WITH DICOUMARIN
TRACY J. PUTNAM, M.D.; LUDWIG V. CHIAVACCI, M.D.; HANS HOFF, M.D.; HYMAN G. WEITZEN, M.D.


Arch Neurol Psychiatry. 1947;57(1):1-13.
ETIOLOGY OF MULTIPLE SCLEROSIS

EVIDENCE has been accumulating over recent years which indicates that vascular destruction, or, more specifically, probably a thrombosis of venules, is an essential link in the chain of causation of multiple sclerosis and the related "encephalomyelitides."1 This evidence may be summarized as follows:

1. Histologic pictures indistinguishable from the lesions of "encephalomyelitis" in the acute stage, and of multiple sclerosis when sufficient time has elapsed to permit gliosis to take place, have been produced experimentally in animals by the retrograde obstruction of cerebral venules2 and by the intravenous injection of various coagulants, especially organ extracts.3

2. Similar lesions are also often seen in pathologic material of human origin, following spontaneous thrombosis of veins of a certain size from any cause, or compression of a pial vein by a tumor.4

3. Thrombi, usually in venules and veins, have been observed in a large . . .

Dicoumarin
An oral anticoagulant that interferes with the metabolism of vitamin K. It is also used in biochemical experiments as an inhibitor of reductases.

Occam's razor (or Ockham's razor[1]), entia non sunt multiplicanda praeter necessitatem, is the principle that "entities must not be multiplied beyond necessity" and the conclusion thereof, that the simplest explanation or strategy tends to be the best one.

Tracy J. Putnam was born in Boston, Massachusetts, on April 14, 1894. Following A.B. (1916) and M.D. (1920) degrees from Harvard
University, his training included neurosurgery under Harvey Cushing at the Peter Bent Brigham Hospital (1925) and neurology with Stanley Cobb at the Boston City Hospital neurological unit (1929-33).Putnam wasdirector of the services of Neurology and Neurological Surgery at the New York Neurological Institute from 1939-47, and Professor of the same disciplines at the College of Physicians and Surgeons, Columbia University. During this period he was a founding member of the National Multiple Sclerosis Society (1946) and what later became the National Epilepsy Foundation (1946)

The bacteriologist and virologist Thomas Milton Rivers spent over thirty years at the Rockefeller Institute as a researcher in the Department of Bacteriology and from 1937-1955, as Director. Working on measles and pneumonia, Rivers discovered the parainfluenzae bacillus and cultivated vaccine virus for human use, and during the 1950s, he played an important role in coordinating research on poliomyelitis as head of the National Institute for Infantile Paralysis. During the Second World War, Rivers led the Naval Medical Research Unit in the South Pacific, rising to the rank of Rear Admiral.
Between 1922 and 1955, Rivers molded Rockefeller into the preeminent laboratory for research on viruses, and in over 100 papers published during these years, Rivers addressed a range of topics relating to some of the most devastating viral diseases, including smallpox, Rift Valley Fever, and epidemic encephalitis. More importantly, he helped delineate the disciplinary boundaries of virology as both conceptually and methodologically distinct.

During the Second World War, Rivers again offered his services, serving as commander of the Naval Medical Research Unit in the South Pacific where his attentions were drawn to coordinating the effort to combat malaria and typhus. He eventually retired from the Navy with the rank of Rear Admiral. He returned to the Rockefeller in 1946, remaining for an additional ten years and eventually earning promotion to director of the institute (1953-1955).

Complexities—and an unrecognized breakthrough

In the decade after World War I, MS research grew more sophisticated. Abnormalities in spinal fluid were noted for the first time in 1919, though their significance was a puzzle. Myelin, which had been discovered in 1878 by Dr. Ranvier, was studied intensively under the microscope and the cell that makes myelin, the oligodendrocyte, was discovered in 1928.

The first electrical recording of nerve transmission, by Lord Edgar Douglas Adrian in 1925, established techniques needed to study the activity of nerves and launched a series of experiments to determine just how the nervous system works. Ultimately, six Nobel Prizes were awarded for these studies. The resulting knowledge included clarification of the role of myelin in nerve conduction and a realization that demyelinated nerves cannot sustain electrical impulses.

At this time, scientists suspected that some form of toxin or poison caused MS. Because most MS damage occurs around blood vessels, it seemed reasonable that a toxin circulating in the bloodstream leaked out into the brain, even though no researcher could find a trace of it.

Just before World War II, an important breakthrough occurred. An animal model of MS was developed out of research on vaccines. It had been known that people vaccinated against viral illnesses, especially rabies, sometimes developed a disease resembling MS. It had been assumed that this occurred because the virus in the vaccines was not completely inactivated.

In 1935, Dr. Thomas Rivers at the Rockefeller Institute in New York City demonstrated that nerve tissue, not viruses, produced the MS-like illness. By injecting myelin he knew to be virus-free into laboratory animals under the proper conditions, he could induce their immune systems to attack their own myelin, producing a disease very similar to MS.

This laboratory animal form of MS, called experimental allergic encephalomyelitis, or EAE, would later become an important model for studying the immunology and treatment of MS. In fact, it paved the way to modern theories of autoimmunity, for it demonstrated how the body can generate an immunologic attack against itself.

But most doctors in the 1930s were still analyzing toxins or checking blood circulation in MS. The importance of EAE to MS was virtually ignored.

Instead, a flurry of experiments in lab animals demonstrated that blocking the blood supply to the brain sometimes caused myelin to die. The damage looked a bit like MS. Doctors wondered if MS was caused by circulation problems, and they tried therapies to stimulate blood flow including blood thinners and drugs to dilate blood vessels. X-rays were also used to treat MS, although more for their novelty than for any sound scientific reason.

It would be many years before the essential similarity of EAE and MS was understood and a link between the immune system and MS was forged.

Reference

Written by Loren A. Rolak, MD. Reproduced by permission from the National Multiple Sclerosis Society, USA. © NMSS, 2003

Instead, a flurry of experiments in lab animals demonstrated that blocking the blood supply to the brain sometimes caused myelin to die. The damage looked a bit like MS. Doctors wondered if MS was caused by circulation problems, and they tried therapies to stimulate blood flow including blood thinners and drugs to dilate blood vessels. X-rays were also used to treat MS, although more for their novelty than for any sound scientific reason.

It would be many years before the essential similarity of EAE and MS was understood and a link between the immune system and MS was forged.

Senator Charles W. Tobey of New Hampshire sponsored the National Multiple Sclerosis Act, which began hearings before the Senate Subcommittee on Health of the Committee on Labor and Public Welfare on May 10, 1949. Senator Tobey's own daughter had multiple sclerosis, and he sought the advice of the National Multiple Sclerosis Society in composing the legislation. When the proposal for a National MS Research Institute was included in hearings on a National Health Plan in the House of Representatives in 1949, Ralph I Straus, the president of the NMMS, gave testimony, as did Senator Tobey, Mrs. Lou Gehrig and Dr. Tracy Putnam, as well as a number of other doctors, family members and patients.

They were not entirely in agreement. Most of the laypeople present sated that no progress whatsoever had ben made in the "fight" against MS and demanded the kind of government interventions that had made possible the mass production of penicillin, which in turn was credited tor the sustained health of Allied troops invading Nazi Europe. Putnam, who had been an active participant in MS research for the last two decades, was confronted by a discontented public who did not seem to know about the progress he and others had achieved since Cruveilhier and Carswell.

Putnam was the first major researcher to go public with a theory of MS cause and the prospect of a treatment in 1942, but in 1949 he could not claim great success for this treatment. Though he described further research into other medications, he was facing people who wanted results, no hypotheses. He was also in private practice and had see the devastation of lives.....

Jugular wrote:........
It would be many years before the essential similarity of EAE and MS was understood and a link between the immune system and MS was forged.

Reference

Written by Loren A. Rolak, MD. Reproduced by permission from the National Multiple Sclerosis Society, USA. © NMSS, 2003

The mastermind behind this compromise was Dr. Putnam, a neurologist, neurosurgeon and psychiatrist who was named head of the Neurological Institute in 1939. A Boston Brahmin, Dr. Putnam was the vice chairman of the National Committee for Resettlement of Foreign Physicians. “It seems likely,” Dr. Rowland concludes, “that all of these European neurologists were appointed by Putnam.”

Dr. Putnam was forced to resign in 1947, ending his career at Columbia. Colleagues at the time suspected several reasons, including a lack of administrative skills, enemies on the staff and the conflicts that arose from having a neurosurgeon running a neurological institute.

But Dr. Rowland unearthed another explanation. A New York newspaper of the era, called PM, reported in 1947 that Dr. Putnam had been told to fire all of the “non-Aryan” neurologists, something he was unwilling to do.

Dr. Rowland corroborated this story when he discovered a 1961 letter written by Dr. Putnam to a fellow physician. Dr. Putnam reported that Charles Cooper, then head of Columbia’s affiliated hospital, Presbyterian, had told him in 1945 “that I should get rid of all the Jews in my department or resign.”

Although Dr. Putnam left, most of the Jewish neurologists stayed, under the leadership of Dr. Merritt. But Columbia did not have a Jewish physician as head of neurology until 1973, when Dr. Rowland was named to the position. He was only the third Jewish clinical chief at the institution.

Quotas for Jewish medical students and physicians disappeared fairly rapidly after World War II, partly in response to Nazi atrocities against the Jews. But Dr. Putnam’s quiet advocacy on behalf of Jewish physicians when such a stance was unpopular should not be forgotten.

The patient first notices a pins-&-needles sensation in his legs. After a time his head and shoulders may twitch, his eyeballs roll wildly, he sees double, reels when walking, stumbles in his speech, from time to time is seized by uncontrollable laughing or crying jags. In advanced stages he may be paralyzed.

The patient is not drunk. These are symptoms of a mysterious, widespread disease known as multiple sclerosis, a disorder of the nervous system. Doctors have recognized it for nearly 100 years (the German poet Heinrich Heine is believed to have died of it), but they have never discovered its cause or cure.

Last week the first concerted attack on the disease was launched by a new organization started by multiple sclerosis sufferers. Based in Manhattan, the Association for Advancement of Research on Multiple Sclerosis has enlisted some of the top U.S. neurologists (honorary chairman: Dr. Tracy J. Putnam, director of Columbia University's Neurological Institute).

Neurologists estimate that multiple sclerosis is more prevalent than infantile paralysis. The disease is characterized by sclerosis (hardening) of scattered patches of nerves in the central nervous system. It has been attributed variously to 1) clots in the small blood vessels of the nervous system; 2) spasmic contractions of the blood vessels;(NOTE FROM ME - ISN'T THIS CCSVI?) 3) a spirochete (not the syphilis variety). But treatments based on these theories (e.g., anti-clotting and blood-vessel dilating drugs) do not cure the disease. It usually strikes between the ages of 20 and 35. It is seldom painful, and rarely fatal, but often cripples its victims.

Prime aims of AARMS: 1) raise funds for a full-dress research program; 2) determine the scope and prevalence of the disease.*

* A substantial number of sclerosis patients turn up in hospitals, but nobody has ever counted the much greater number who are treated at home by private doctors.