When University of Cambridge neurobiologist Jenny Morton began working with sheep five years ago, she anticipated docile, dull creatures. Instead she discovered that sheep are complex and curious. Morton, who studies neurodegenerative diseases such as Huntington's, is helping evaluate sheep as new large animal models for human brain diseases.

Huntington's is a fatal, hereditary illness that causes a cascade of cell death in the brain's basal ganglia region. The idea to use sheep to study this disease arose in 1993 in New Zealand, a country where sheep outnumber humans seven to one. Researchers had already identified disorders shared by humans and sheep, but University of Auckland neuroscientist Richard Faull and geneticist Russell Snell had a more ambitious notion. They decided to develop a line of sheep carrying Huntington's, which is brought on by repeats within the gene IT15, in the hopes of studying the condition's progression and developing a treatment. They accomplished their goal in 2006 after extensive efforts.

Why sheep? For one, they have big brains—comparable to macaques, which are the only other large animals currently used to study this disease—with developed, cortical folding like our own. Also, sheep can be kept in large paddocks with their fellows and monitored remotely via data-logger backpacks, allowing scientists to study these creatures in a natural setting with fewer ethical concerns than studying caged primates. What is more, these long-lived, social animals are active and expressive, recognize faces, and have long memories. They also learn quickly and engage in experiments readily. This has allowed Morton to develop cognitive tests similar to those given to humans. The researchers can study the full progression of Huntington's—which in humans is associated with gradual mental and motor decline—and compare the changes with the normal functioning of healthy individuals.

This spring Faull, Snell, Morton and their colleagues will begin monitoring two flocks of Huntington's sheep in Australia. One flock will be inoculated with one of the most promising therapies yet devised—a virus that silences IT15's mutations—and the other will serve as the control. Currently no cure exists for any human brain disease. The researchers believe these studies could be a milestone. “The tragedy of this disease is enormous. It's a curse on the family,” Faull says. “Maybe we can lift that curse.”