THE VIRAL

BRAIN

Scientists may need to seriously reconsider

the cast-aside hypothesis that pathogens can

play a part in neurodegenerative diseases.

BY ASHLEY YEAGER

A

little more than 10 years ago, when neurobiologist

Richard Smeyne was working at St. Jude Children’s

Research Hospital in Memphis, he saw a video of a

duck acting strangely. The white-feathered, orange-

billed bird was standing slightly apart from its flock on a farm

in Laos. It walked in circles and flipped up a wing, then lost

its balance and fell over. It got up, tried to flap both wings, and

fell over again.

Smeyne saw the video while attending a seminar being given

by then-postdoc David Boltz and Boltz’s advisor, a “flu hunter”

named Robert Webster, who headed the influenza research pro-

gram at the hospital. The duck, Boltz and Webster explained, was

infected with the H5N1 bird flu virus that had sickened thou-

sands of birds and killed hundreds of people in 2006 and 2007.

Smeyne, who had been studying the neurobiology of Parkinson’s

disease in mice, recognized the animal’s motor issues. That duck

has Parkinson’s, he thought.

He told Webster this after the seminar, and Webster

laughed, Smeyne recalls. “He said, ‘Well, it’s a sick bird.’” But

Smeyne was curious about the neural mechanisms underlying

the duck’s abnormal behavior.

He wondered if healthy ducks infected with H5N1 in the

lab would show Parkinson’s-like neurodegeneration. In St.

Jude’s biosafety level 3 lab, he and his colleagues infected

ducks with the virus, then sacrificed the birds and removed

their brains, storing them in formaldehyde for three weeks to

kill the active virus.

When Smeyne began to dissect the once-infected duck brains,

he focused on a region called the substantia nigra, which is often

damaged in Parkinson’s patients. “When I opened it up, when I

cut the brain, the substantia nigra was devastated. All the neu-

rons were completely gone,” Smeyne says. He went back to Web-

ster, he recalls, and said, “I wasn’t wrong. Your duck does have

Parkinson’s disease.”

Because the bird had had the flu, Smeyne wondered whether

there was a connection between the viral infection and the exten-

sive neurodegeneration he observed. He asked Webster about the

symptoms experienced by people infected with H5N1. Webster’s

answer—inflammation of the brain that leads to tremors and

other motor malfunctions—didn’t sound like “full-blown Parkin-

son’s disease,” Smeyne says, “but it was parkinsonism,” a subset of

symptoms of the disease.