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. This later led to research on viral causes of MS.
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. With this new technology now available, 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 described the inflammation around blood vessels and the damage to the myelin with a clarity and thoroughness that 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.
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. Louis Ranvier, was studied intensively under the microscope and the cells that make myelin (the oligodendrocytes) were 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 transmit impulses efficiently.
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, and so it attacked the myelin. In 1935, Dr. Thomas Rivers at the Rockefeller Institute in New York City, demonstrated that immune cells, 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 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”—the process by which the body generates an immunologic attack against itself. But most doctors in the 1930s were still analysing toxins in MS and the importance of EAE was overlooked. It would be many years before the similarity of EAE and MS was understood and a link between the immune system and MS was forged.
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 abandoned their search for toxins and instead wondered if MS was caused by circulation problems. So 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.
World War II focused the energies of the scientific world on new technologies, and research continued despite the global upheaval. In 1943, for example, the actual composition of myelin was determined. An unforeseen consequence of World War II was the availability of medical information on the huge population of young men who had served in the military. Studying their MS, doctors discovered the uneven distribution of the disease. A strong geographical gradient was apparent, showing that the incidence and prevalence of MS increased steadily as one moved northward away from the equator.
Meanwhile, the immune system became an object of intense scientific study. Special immunological white blood cells called B cells were discovered and shown to produce proteins called antibodies. It was soon learned that antibodies neutralize viruses but are also capable of attacking the body’s own tissues. It seemed that B cells also produced the oligoclonal bands in MS spinal fluid.
There were more studies of EAE. Experiments showed that EAE could be transmitted by transferring T cells (another type of immunological white blood cell) from an affected animal to a well one, showing that EAE was an immune disease. And at last, scientists recognized that EAE was in many ways a model of human MS.
However, beyond the world of research, doctors who treated people with MS in the 1950s continued to suspect the cause lay in impaired blood flow, so circulation stimulators still dominated treatment. Nevertheless, doctors had not yet thought to analyse these therapies with controlled studies to track the results, so no reproducible or valid information could emerge about their safety or effectiveness. Treatments were still based more on opinions than facts.
In 1953, one of the major medical breakthroughs of the century occurred with the Nobel Prize-winning description of the structure of DNA by Francis Crick and James Watson. The way in which genes control biologic functions became clearer, including how the immune system is regulated by sequences of genes.
Additional studies on nerve conduction showed how chemicals generate electricity as they flow through channels in the nerve fiber membranes. And myelin was further broken down into its components, isolating the basic protein suspected to be the target of the MS attack.
Scientists studied B-cells, T-cells, genes, and myelin but without uncovering a clear unifying thread to direct MS treatment. The emerging scientific complexity of MS confused rather than clarified, and research gave doctors very little guidance on what was best for their patients.
With the ability now to make an accurate diagnosis and measure how therapies affected disability, it was possible to begin scientifically testing MS treatments. A group of patients who were having exacerbations— or acute attacks of their MS—were given adrenocorticotropic hormone (ACTH), which is a hormone normally produced by the pituitary gland.
It stimulates production of steroids by the adrenal glands. Increased secretion of these natural steroids provides an anti-inflammatory and immune suppressing effect. The ACTH group was compared to a similar group that received a placebo (an inactive look-alike substance).
The ACTH proved superior in speeding recovery. In subsequent years, treatment with ACTH was replaced by the high-dose, intravenous steroid therapy that is in use today for acute exacerbations. This 1969 study was the first to prove that a therapy could be developed that would improve the symptoms of MS. For the first time, there was a scientific treatment for MS.
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