The history of multiple sclerosis.

A promising start

With remarkable foresight, the very first research grant from what was then called The Society for the Advancement of Multiple Sclerosis Research was awarded to study the immunology of MS -- the relationship between the body's immune defense system and the impact of MS on the central nervous system (the brain and spinal cord).

This 1947 grant went to Dr. Elvin Kabat at Columbia University. He subsequently identified abnormal immunologic proteins in the spinal fluid of people with MS. In lab tests, these proteins appeared as patterns known as oligoclonal bands. Oligocional bands not only proved to be a valuable diagnostic test for MS but also a major demonstration that MS and the immune system are connected.

A world-wide research effort begins

In the next few years, the renamed National Multiple Sclerosis Society awarded grants to scientists in 17 countries in all fields of medicine, pushing forward research that ranged from description to diagnosis and from finding a cause to searching for a cure.

Recipients of early NMSS grants included Dr. Jonas Salk for studies on the immunology of MS and Dr. Rita Levi-Montalcini, who later won the Nobel Prize for describing proteins that help nerve cells grow and stay healthy.

A new major partner

In 1950, in a bold move, the new Society persuaded Congress to establish a special section of the National Institutes of Health. With the birth of what is now called the National Institute for Neurologic Disorders and Stroke (NINDS), the movement against MS gained one of its most essential partners. NINDS and NMSS -- along with members of the International Federation of MS Societies, which was also founded by Sylvia Lawry in 1967, have supported virtually every major MS study from that day to this.

New research directions

An unforeseen consequence of World War 11 was the availability of medical information on a huge population of young men who had served in the military. For the first time, the uneven distribution of MS was appreciated. A strong geographical gradient was apparent, showing that the incidence and prevalence of MS increased steadily as one moved northward or southward away from the equator.

Meanwhile, the immune system became an object of intense scientific study. Special white blood cells called B cells were discovered and shown to produce proteins called antibodies. It was soon learned that antibodies neutralize viruses and other infectious agents. Antibodies are also capable of attacking the body's own tissues.

There were more studies of experimental allergic encephalomyelitis, or EAE, a disease first identified in laboratory rodents. For example, experiments showed that EAE could be transmitted by transferring T cells (another type of white blood cell) from an affected animal to a well one, showing that it was an autoimmune disease. And at last, scientists recognized that EAE was in many ways an excellent model of human MS.

But, 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 dominated treatment. These therapies were used without controlled studies to track the results, called clinical trials, so no reproducible or valid information could emerge about their effectiveness.

Breakthroughs expand knowledge but increase confusion

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 lames Watson. The way in which genes control biologic functions became clearer -- including how viruses work and how the immune system is regulated.

Additional studies on nerve conduction showed how chemicals generate electricity as they flow through channels in nerve endings. And myelin was broken down into its components, isolating the basic protein suspected to be the target of the MS attack.

This era saw scientists striking out on many different paths, testing many possibilities, and formulating many new theories, but without uncovering a clear unifying thread to direct MS treatment. Meanwhile, doctors continued to struggle with the challenge of diagnosing and treating people with MS. The emerging scientific complexity of MS confused rather than clarified their challenge. So while much was being learned, research could give doctors very little guidance on what was best for their patients.

Chaos addressed by the NMSS

Some in the MS community were disaffected by this situation. They felt the MS movement should concentrate solely on services for people living with MS. Perhaps the mystery was too complex to be solved. The National MS Society, which by 1960 had established 1 14 local chapters to provide services for individuals and families, kept up the scientific assault.

To bring order to the medical management of MS, the Society funded a panel of experts, headed by Dr. George Schumacher, to draw up standard guidelines for MS diagnosis. Although they have been refined since, these standards are still in use today. At the same time, a rating scale for determining the level of disability and the parts of the nervous system affected by MS was refined by Dr. John Kurtzke.

Having standards helped doctors make earlier, more accurate diagnoses and allowed research on treatments to be done with greater reliability.

The first valid scientific trial

The year 1969 saw the first successful scientific clinical trial of a treatment in the history of MS. A group of patients who were having exacerbations -- or acute attacks of their MS -- were given the steroid ACTH. Their experience was compared to that of a similar group who received a placebo (an inert lookalike). The ACTH proved superior in speeding recovery. This primitive intramuscular steroid therapy would give way to the modem steroid therapy still in use today for acute exacerbations.

This trial used the new rating scales and diagnostic standards to ensure that results seen in the treated and untreated groups could be compared accurately. The way to solid progress was now open.

Dr. Rolak, a neurologist, treats people with MS at the Marshfield Clinic in Marshfield, Wisconsin.