For all the worry mad cow disease is generating, it's just one in a family of 10 diseases discovered so far — five in animals, five in humans — that are arguably medicine's most mystifying maladies.
Most so-called prion diseases (search) are incredibly rare in this country, although one has spread into deer and elk herds in at least 12 states, sparking concern about contaminated game meat.
Yet scientists can't answer the most basic questions about prions, even though learning how the rogue proteins cause sponge-like holes in brains could improve understanding of more common neurodegenerative diseases like Alzheimer's.
Because they're not considered a big threat here, few U.S. scientists study prions. The National Institutes of Health (search) spent $29.4 million on prion research last year; most goes to just two laboratories.
Europe, where mad cow disease devastated the beef industry in the 1990s, spends almost 10 times as much, says Dr. Richard T. Johnson of Johns Hopkins University, who led an exhaustive review of prion research for the Institute of Medicine.
Then there's tracking. The United States spends about a penny per person on surveillance for human versions including the classic Creutzfeldt-Jakob disease (search) that hits 250 Americans a year and the "variant CJD" linked to mad cow-tainted beef, so far not found here.
Britain, where variant CJD first appeared, spends about a nickel per person on surveillance.
As for testing, Congress did designate a National Prion Research Project (search) in 2002 to develop ways to diagnose prion diseases before the person or animal dies. But funding wasn't renewed for the Defense Department-run project last year. For now, 35 scientists are sharing $37 million in the hunt — even as the Institute of Medicine predicts it will take a major leap in innovation to find a better test.
Still, research grants aren't the chief obstacle to researching these "transmissible spongiform encephalopathies," or TSEs. Double the money today and scientists couldn't use it all, Johnson says, because too few laboratories can spend years waiting for the slow-growing diseases to sicken test animals — or safely handle highly infectious prions.
How infectious? Burning tainted animal tissue into ash doesn't destroy them. Chemical disinfectants don't work well, either. And prions cling to the glass and steel in operating rooms and labs where diseased brains must be cut for diagnosis and study.
Adding to the complexity, each TSE is somewhat different. Mad cows aren't considered contagious, for instance. But the nation's most common TSE, chronic wasting disease in deer and elk, is. Nobody's sure exactly how CWD spreads from animal to animal, but urine and saliva are top suspects.
"To be perfectly honest, I'm more worried about chronic wasting disease as a potential public health problem than mad cow," says Johnson. European scientists "shake their heads and say, 'Why aren't you Americans working on this, you're sitting on a powder keg.'"
TSEs arise when a protein the body normally harbors folds into an abnormal shape, setting off a chain reaction of misfolds that eventually leaves clumps of dead brain cells. There's no foreign invader for the immune system to catch and prions contain no genetic material, so standard ways to diagnose, treat and prevent disease so far don't work.
The TSE family includes:
— Scrapie, the sheep version, first described in the 18th century.
— Mad cow disease, or bovine spongiform encephalopathy, believed spread when cows ate feed contaminated initially with scrapie and then with BSE-tainted cow tissue. Such feed was outlawed here in 1997; the mad cow discovered last month in Washington state was born shortly before that ban.
— Classic CJD, a quickly fatal human dementia known for 80 years. Most cases are sporadic, their cause unknown; some are inherited; some are spread through infected surgical equipment, tissue transplants or hormones.
— Variant CJD, the different version linked to tainted beef.
— Other human forms include kuru, discovered in cannibals in Papua New Guinea; and fatal familial insomnia and Gerstmann-Straussler-Scheinker disease, both genetic.
— In animals, chronic wasting disease isn't known to spread to people but health experts advise against eating infected deer or elk.
— Mink and cats also get TSEs linked to infected feed.
The Institute of Medicine, at the Defense Department's request, recently recommended a range of prion research priorities — from intense study of chronic wasting disease's true threat to better surveillance in case completely new TSEs arise.
A major focus should be simply how prions work, the report stresses — because more common neurodegeneration, like Alzheimer's, occurs when other proteins run amok, too.
"What's interesting is the traffic of proteins," Johnson says. "It's a great biological question, and answering those questions may give us insights into big important diseases."