Ryan Grant was in his twenties and serving in the military when he learned that the numbness and tingling in his hands and feet, as well as his unflinching fatigue, were symptoms of multiple sclerosis. Like nearly a million other people with MS in the United States, Grant felt as though his immune system was attacking his central nervous system. The insulation around his nerves crumbled, weakening the signals between his brain and body.
The disease can have a wide variety of symptoms and consequences. Grant is now 43 and can no longer walk, and has moved to a Veterans Home in Oregon so that his wife and children don’t have to be his caretakers. He knows the course of the disease all too well and can name risk factors that he shared and did not share with other MS patients, three-quarters of whom are female. But until recently, he hadn’t heard that many scientists now believe that the main factor behind MS is a virus.
For decades, researchers suspected that the Epstein-Barr virus, a common infection in children, is linked to multiple sclerosis. In January, Science magazine made the headlines when it published the results of a 20-year study of people who, like Grant, had served in the military. The study’s researchers concluded that EBV infection is “the leading cause” of MS.
Bruce Bebo, executive vice president of research at the nonprofit National Multiple Sclerosis Society, which helped fund the study, said he believes the findings just fall short of proving causation. However, they provide “probably the strongest evidence to date of that link between EBV and MS,” he said.
The Epstein-Barr virus has infected about 95 percent of adults. Yet only a small proportion of them will develop multiple sclerosis. Other factors are also known to influence a person’s MS risk, including genetics, low vitamin D, smoking, and childhood obesity. If this virus that infects nearly everyone on Earth causes multiple sclerosis, it is doing so along with other actors in a choreography that scientists do not yet understand.
Amid that lingering uncertainty, scientists are debating how to move forward from here. Antivirals or drugs that target infected cells, some of which are already in development, may help MS patients. Vaccines against EBV are also under development. The authors of the Science article say widespread vaccination can prevent most cases of MS. But other researchers aren’t so sure the case is closed and suggest putting more emphasis on understanding how the virus may interact with social factors like stress.
“Patients often want to know why this disease happened to them,” says Lindsey Wooliscroft, a neurologist and associate director of research for the VA’s Multiple Sclerosis Center of Excellence in Portland, Oregon. “It’s frustrating when I can’t tell them.”
Epstein-Barr usually strikes in early childhood, with few or no noticeable symptoms. After the initial infection, the virus lurks in certain immune cells for the rest of a person’s life.
If someone avoids EBV until adolescence or adulthood, the virus is more likely to cause mononucleosis, an illness characterized by fever and fatigue. Mono is more common in Western countries, where children encounter fewer germs at a young age, said Alberto Ascherio, a professor of epidemiology and nutrition at the Harvard T.H. Chan School of Public Health and senior author of the Science paper.
Like mono, multiple sclerosis is most common in the US and parts of Europe. Scientists first suggested more than four decades ago that the two conditions may be related. In the years that followed, the evidence piled up: Almost everyone with multiple sclerosis has latent EBV in their cells. People who remember being sick with mono have an increased risk of MS. Immune cells harboring the virus are more common in the brains of MS patients.
“We have long suspected that the Epstein-Barr virus played a role” in the development of MS, Wooliscroft said. “But it was just really hard to prove.”
The surest way to prove causation would be to start with a group of healthy, uninfected adults and randomly divide them into two groups. Researchers would infect only one group with the virus and then monitor both groups to see who develops MS.
In the real world, such an experiment is not ethical. Ascherio and his co-authors wanted to get the closest: find a group of people who had not yet been infected with EBV at a certain point in time, and then see if those who eventually did become infected were more likely to develop MS. “Conceptually, our study is very simple,” Ascherio said. “In practice, it seemed virtually impossible to implement.”
That’s because the scientists need a large number of study participants to monitor over years, since MS can be slow to develop and diagnose. For help, the research team turned to the US military, which regularly collects blood samples from active-duty military personnel for HIV screening. In the end, it took the team two decades to collect enough data to perform the statistical analysis.
