The history of multiple sclerosis, part III.

MS affects people of all ages, around the world. History shows that MS was written about as long ago as the Middle Ages, but detective work on the cause and cure only began with the development of scientific medicine about 100 years ago. This brings the story to the present, the 50th year of the National MS Society.

1960-1970

During the 1960s, scientific research into the cause of MS came to focus on two main lines of inquiry, which are still being explored today.

The first emerged from a finding about the immune system. White blood cells that react against myelin, specifically against a major component called myelin basic protein, were discovered in the animal form of MS, called EAE (experimental autoimmune encephalomyelitis) and in human MS. This led scientists to consider the possibility that MS involves a direct immune-system attack on myelin.

The second idea came from another finding. Studies showed that people with MS have altered antibodies against viruses. This revived the older thinking that MS could be caused by a virus. But rather than a viral infection directly damaging the central nervous System, viruses might alter the immune system and trigger it to damage myelin.

These two ideas remain closely mingled today: MS may combine features of both an infectious and an autoimmune disease.

1970-1980

Understanding of immunology was enhanced as doctors learned to prevent the immune system from rejecting transplanted foreign organs. Insights from successes in transplantation, as well as intensive studies of EAE, further linked MS to the part of the immune system that makes tissues compatible with each other.

In 1978, the first CT scans were done on people with MS. And, in 1979, a Nobel prize was awarded for development of this powerful new tool. CT scans use a computer to link a circular array of x-ray images to create detailed pictures of the human brain. The diagnosis of MS was further improved with the introduction of tests called evoked potentials, which measure nerve conduction.

Scientific research began to yield direct therapeutic dividends as well. Steroids to suppress immune activity were now widely used to treat MS attacks, and the first small studies were performed using interferons, substances that modulate the immune system. The first studies of beta interferon for MS began at the end of the 1970s.

In 1970, scientists studying EAE in lab animals suspected that some myelin protein fragments prevented the disease and actually seemed to protect the animals. Spurred by this finding, they synthesized a mix of protein fragments and used it to treat first animals and then humans with MS. The product was named copolymer 1 (and is now manufactured under the name Copaxone).

1980-1990

Scientists began to understand in more detail how white blood cells are activated by foreign substances to mount attacks. One activating trigger can be a virus.

Doctors also learned that parts of some viruses look so much like normal human tissue that white blood cells will inadvertently attack them when they attack the virus. This is yet another mechanism by which viral infections could lead indirectly to destruction of myelin.

At about the same time, the white blood cell type that causes the actual damage to myelin in MS was finally identified. It is the macrophage (or "Big Eater" in Greek).

The first studies of identical and fraternal twins, begun in this decade, extended knowledge about the genetics of MS. And psychosocial and mental health issues, as well as the cognitive changes occasionally caused by MS, began receiving long overdue research attention.

CT scanning was surpassed by a new technology, the MRI scan, which showed the brain in greater detail. The first MRI scans of people with MS were performed in 1981 by Dr. I. R. Young, in England. By 1984, it became apparent that the MRI could actually see MS attacks within the brain, including many which did not cause any symptoms. MRI changed the basic understanding of MS, for by 1988 sequential MRI scans proved that MS is a constant, ongoing disease even though symptoms may be appearing only sporadically.

The 1980s may legitimately be called the "treatment decade" in MS. There was an explosion of clinical trials. Guided by the National MS Society, scientists reached a consensus on the design and conduct of research for new treatments. For the first time the emphasis could shift away from palliation, where the aim is to help people with MS feel as good as possible for as long as possible, and go instead toward attempts to control or cure the underlying MS.

Major clinical trials conducted during this decade led to approvals of the first drugs in history shown to affect the course of this disease.

1990-1996

Today, the therapeutic momentum is sustained and growing. In 1993, Betaseron was approved by the FDA to reduce the severity and frequency of attacks. In 1996, Avonex was approved to slow the development of disability and reduce the severity and frequency of attacks. At last, decades of research are being rewarded with some practical treatments for the disease.

Many newer immunologic therapies are under investigation, including intravenous immunoglobulins. Trials of Linomide, cladribine, and Betaseron for people with progressive MS -- the forms of the disease that do not have a pattern of attacks and recovery -- are underway. Exciting areas of exploration include laboratory studies on remyelination and the possibility of one day being able to stimulate recovery from existing damage.

And through the years, life for people with MS has steadily improved. In 1890, when MS was treated with herbs and bedrest, life expectancy was five years. By 1970, when steroids were the major available medication, life expectancy was about 32 years from time of diagnosis. Today, with an array of medications and greatly improved nursing care, life expectancy is essentially normal.

The decade is coming when we will be able to write a final chapter of this story. The Society will have completed its mission and MS will be history.

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