The History of
MS: The Basic Facts
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The history of
multiple sclerosis (MS) is a detective story spanning more than a century.
Many clues have been pieced together, but only now are answers emerging. To
appreciate why the trail to a solution has been so long and hard, it is
necessary to understand what we scientists now believe to be true about MS.
Multiple sclerosis is one of the most common diseases of the nervous system, afflicting people
of virtually all ages around the world, although it has a special preference
for young people, especially women, and for those who grew up in northern
We believe MS involves
a genetic susceptibility, but it is not directly inherited. It usually causes sudden
neurologic symptoms including vision loss, paralysis, numbness, and walking difficulties. The
symptoms can be diverse and confusing, often coming and going without any
pattern, making it difficult to diagnose, even today.
The symptoms appear
because nerves in the brain and spinal cord lose their ability to transmit
signals. Myelin, a complex substance that surrounds and insulates nerve
fibers, is essential for nerves to conduct electricity and carry out their
function. Myelin is destroyed in MS.
In MS, cells and
proteins of the body’s immune system, which normally defend the body against
infections, leave the blood vessels serving the central nervous system, pour
into the brain and spinal cord, and destroy myelin. The specific triggering
mechanism that causes an immune system to attack its own myelin remains
unknown, although a viral infection on top of an inherited genetic
susceptibility is a leading suspect.
discovery of MS
Until the early years
of the 19th century,
physicians relied on superstition, hearsay, and the wisdom of the ancients to
care for the sick. Medical ideas were not scientifically tested. Even so,
physicians were sometimes good observers and we can identify people who
undoubtedly had MS from descriptions written as long ago as the Middle Ages.
MS has always been with us.
Once the scientific
method took hold in medicine, MS was among the first diseases to be described
scientifically. The 19th-century
doctors did not understand what they saw and recorded, but drawings from
autopsies done as early as 1838 clearly show what we today recognize as MS.
Then, in 1868,
Jean-Martin Charcot, a professor of neurology at the University of Paris who
has been called “the father of neurology,” carefully examined a young woman
with a tremor of a sort he had never seen before. He noted her other
neurological problems including slurred speech and abnormal eye movements,
and compared them to other patients he had seen. When she died, he examined
her brain and found the characteristic scars or “plaques” of MS.
Dr. Charcot wrote a
complete description of the disease and the changes in the brain that
accompany it. However, he was baffled by its cause and frustrated by its
resistance to all of his treatments. These included electrical stimulation
and strychnine—because this poison is a nerve stimulant. He also tried
injections of gold and silver, as they were somewhat helpful in the other
major nerve disorder common at that time—syphilis.
A prisoner of
In the last decades of
the 19th century,
the leading physicians of the world came to understand that MS was a specific
disease. MS was recognized in England by Dr. William Moxon in 1873, and in
the United States by Dr. Edward Seguin in 1878. By the end of the century,
much of what can be learned about MS from careful observation was known: that
the disease is more common in women than men, that it is not directly
inherited, and that it can produce many different neurological symptoms.
But observation can go
only so far. Knowledge of MS could not advance without deeper understanding
of biology and better research tools. The very existence of the immune system
was unknown. Doctors of the time assumed the same disease rarely struck the
same person twice because a disease “used up” the materials in the body it
needed to live, much the way crops use up soil nutrients and die unless they
In the 19th century, scientists first learned that
bacteria cause many diseases. As the 20th century began, they discovered even
smaller organisms, viruses, and developed techniques for growing and studying
bacteria and viruses in the laboratory.
In 1906, the Nobel
Prize for Medicine was awarded to Dr. Camillo Golgi and Dr. Santiago Ramon y
Cajal, who perfected new chemicals to enhance the visibility of nerve cells
under the microscope. Equipped with this new technology, Dr. James Dawson at
the University of Edinburgh in 1916 performed detailed microscopic
examinations of the brains of patients who had died with MS.
Dr. Dawson wrote a
description of the inflammation around blood vessels and the damage to the
myelin with a clarity and thoroughness which has never been improved upon.
But so little was known about the brain’s function that the meaning of these
changes could only be guessed at.
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.
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Copyright © National Multiple
Sclerosis Society, 2003