Family curse reveals emerging threat

SCIENCE | The Family That Couldn't Sleep: A Medical Mystery by D.T. Max. Random House, $25.95, 299 pages.

For more than two centuries, members of a Venetian family have suffered from insomnia. This was not your run-of-the-mill, watching infomercials at 4 a.m. variety. Instead, usually in middle age, they begin to stay awake for days on end. Their minds go haywire and their bodies deteriorate. Before long, they die. For a long time, family curse was the best explanation for their condition.

Then, in 1997, researchers discovered their cause -- proteins that have gone awry in the brain. These "prions" fuel neurological diseases that have killed millions of sheep and cows and almost wiped out a tribe in Papua, New Guinea, through a brain-eating disease whose only visible symptom was uncontrollable laughter. Prions may also unlock the key to cures for far more common diseases including Alzheimer's and Parkinson's.

Science writer D.T. Max explores the history of prions, and the threat they pose in "The Family That Couldn't Sleep: A Medical Mystery." Interweaving case histories with gripping accounts of cutting-edge research, Max puts a human face on the complex systems of the human body. It is an important book, because degenerative diseases are becoming more common, and new protein-based diseases are likely to emerge and threaten us. It is also deeply moving because Max has a personal stake in this topic: He must wear braces on his weakening legs because of a mysterious protein-related disease.

Max reveals his illness when he meets the afflicted Italian family in 2001 (he changes their names to protect their privacy). Lisi, a nurse, and her husband, Ignazio, a physician, recall the terrifying days in 1986 when Lisi's Uncle Silvano started to sweat and his pupils turned to pinpricks. They knew the worst was yet to come. Though he died like many of Lisi's relatives before him, the journey of his remains was different.

Two scientists examined his brain and discovered his thalamus had been eaten away, allowing body functions to fire continuously and making healing sleep impossible. They had a name for his disease -- Fatal Familiar Insomnia -- but little understanding of its cause, much less a treatment or cure.

While living in fear that she too would become ill in this bizarre fashion, Lisi worked with Ignazio to make a family tree revealing both the frequency and rarity of FFI. Only 30 million people worldwide suffer from FFI, but in families with the affliction, their offspring have a 50 percent chance of inheriting the condition.

The two scientists who studied Uncle Silvano -- Pierluigi Gambetti and Elio Lugaresi -- relayed their findings to an American colleague, a biochemist named Stanley Prusiner. His subsequent work earned him the Nobel Prize for Medicine in 1997.

Prusiner elicits mixed feelings. Max calls him reckless in relating to other scientists and describes his anger and haughtiness. Max uses his outsize personality to give us a peek into the competitive world of modern science, complete with large egos and uncompromising ambition.

Scientists routinely classify infections under three types: bacterial, viral or fungal. Prusiner isolated a new disease-causing agent: the "prion" (short for "proteinaceous infectious particle"). Prions can enter the brain through infection or can come from a mutation in the gene that encodes the protein. In the brain, prions cause normal proteins to refold abnormally; when these multiply, they accumulate and destroy nerves. Eventually the brain is riddled with holes.