On the Heels of MS

Donald H. Gilden, ’63, knew the moment he touched the dying man’s cold hand he wanted to become a doctor. He was just five years old when he made his decision. His grandfather had taken him to visit a friend who was dying of congestive heart failure and was surviving in an oxygen tent. Young Gilden was under strict orders not to disturb the man, but he disobeyed his grandfather slipping his hand under the tent. The old man squeezed the boy’s fingers and told him stories about his grandfather.

“After that day I never stopped talking about it,” says Gilden, professor and chairman of the department of neurology and professor of microbiology at the University of Colorado School of Medicine. “I was going to be a doctor when I grew up. I never wanted to do anything else.”

Gilden, age 70, has indeed made his mark on the profession. He is recognized as a pioneer in the field of neurovirology for groundbreaking work relating to shingles and multiple sclerosis (MS).

After nearly 150 years of medical speculation, Gilden discovered that varicella zoster virus—the virus that causes shingles—is latent in human ganglia. More than a million people a year suffer from shingles, and his work helped lead to a shingles vaccination.

He has also been working to track down the virus he believes causes MS, a disease that affects about a quarter of a million people in the United States. But this has been far more challenging. Yet Gilden is focused on what he wants to accomplish and understands that it will perhaps take the rest of his life, or even longer, to reach answers. “You have to be patient,” he says. “Science goes little by little. Progress is little by little.”

For his work, Gilden has received an alumni award for distinguished service from the University of Chicago School of Medicine, the International Society for NeuroVirology Pioneer Award, and, in May, he will receive the Medical Alumni Association’s Honor Award and Gold Key, presented for outstanding medical accomplishments and distinguished service to mankind.

A neurologist by training, Gilden sees patients who suffer from migraines, multiple sclerosis, Alzheimer’s, stroke, and Parkinson’s. “I will see anyone,” he says. “Clinical neurology has always been one of my first loves.” But most of his time is spent in the lab conducting research in the microscopic world of DNA, RNA, viruses, and proteins. “Sometimes in the lab my head is spinning because we have big things going on,” Gilden says.

As a boy growing up in Baltimore, Gilden’s world revolved around school and working summers in the family business, Sam Gilden & Son, a wholesale store that supplied hair tonic, razor blades, bobby pins, toothpaste, and other items to local drug stores. He unloaded trucks, packed orders, swept floors, and, when he was old enough, made deliveries in a bright red Dodge delivery truck His father saw him taking over the business one day, a task which demanded hard work and long hours. “We never had dinner with my father,” Gilden recalls. “The wholesale business was a tough business.”
Gilden’s real “job” was to go to school, and he excelled in biology, chemistry, and math. Classes in foreign language, however, barely held his interest. “For me the language of medicine was all I ever cared about,” he says.

He graduated from Dartmouth College in 1959, and moved back home to go to medical school. Gilden interned at the University of Illinois Hospital in Chicago, and did his residency in neurology at the University of Chicago Hospitals.
It was in the late 1960s while he was a staff neurologist in the U.S. Army at Walter Reed Army Medical Center in Washington, D.C., that he became interested in research. After seeing patients during the day, he had time to catch his breath in the evening and mull over the amazing research underway. Researchers had discovered that measles virus in the brain could cause chronic encephalitis, and that Jakob-Creutzfeld disease—a “degenerative” brain disorder in humans—was infectious.

“I said to my wife, ‘I think I want to do a fellowship in infectious diseases,’” recalls Gilden, who was 32 at the time. “She looked at me like she married a crazy man.”
He was accepted at the Johns Hopkins University School of Hygiene and Public Health as a postdoctoral National Institutes of Health fellow. After about three years, he joined the faculty at University of Pennsylvania and set up a lab at the Wistar Institute in Philadelphia to find the virus that causes MS.

He worked closely with MS patients who lived in a chronic care facility and were ravaged by the disease. Gilden asked if they would donate their brains after death to his research because he was looking for the cause of MS. Sometimes his phone rang in the middle of the night and within an hour Gilden was harvesting brain from their skulls. “I had my own saw,” he says.

He studied 24 brains over eight years, but never found the MS virus. So, he turned his attention to varicella zoster virus, which causes chickenpox in children and shingles in adults. Nobody had ever isolated the virus, and if he could prove it was there he believed he could use the same technique to find the MS virus.

He tore into his work mapping the viral genome in human ganglia along the entire nervous system. In 1983, he proved for the first time that the virus was latent in ganglia and “reawakens” causing shingles. The shingles virus causes pain and even stroke if it makes its way to the brain.
Gilden found several other diseases caused by the virus, such as zoster sine herpete, or shingles without the rash. His discoveries led to more work for his team. Gilden left the University of Pennsylvania in 1985 to become professor and chairman of the department of neurology at the University of Colorado School of Medicine and professor of microbiology.
At the University of Colorado, 15 members of Gilden’s team are working on varicella zoster virus and MS. They harvest ganglia collected from an autopsy room. “We go there every day,” Gilden says. “If it is a good case we will go as far as we have to. We even get specimens from Japan.”

MS has been a hard case to crack, but Gilden seems to be making progress. The common theory is that MS is autoimmune. The body’s immune response attacks a protein that is normally in the brain. The attack is so violent and persistent that the brain is destroyed in the process.

“We don’t think that is the case at all,” Gilden says. “Even now we have evidence that it is not autoimmune.” He argues that in people with MS who have increased amounts of an antibody called immunoglobulin G (IgG), in their brain and spinal fluid, the IgG is directed against an infectious agent, but nobody is quite sure at what agent it is directed.
He and his team are looking for footprints of virus in MS. “We are writing a paper showing that the immune response in MS is not against a self (auto) protein,” he says.

While he is busy with his research, Gilden, who is married and has three adult sons, skis and plays the violin—a 1779 Guadagnini. He is also quick to tell a joke.

Gilden would like to find out what causes MS and how to prevent varicella zoster virus from reactivating. He is unfazed by the fact that his research into MS and varicella zoster could take the rest of his life. “It’s exciting,” Gilden says. “I feel privileged.”

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