California scientists say they have created the first synthetic version of a rogue protein called a prion and used it to give mice a brain-destroying infection, evidence important to settling any lingering doubt these mysterious substances alone cause mad cow disease and similar illnesses.
The report, published Thursday, won’t end the scientific controversy, as skeptics already are criticizing the research.
But if the work ultimately is validated it could have far-reaching implications — such as helping to create diagnostic tests for mad cow disease. It also could help explain why normal brain proteins suddenly go bad and sicken some people who’ve never eaten mad cow-tainted food.
'A renaissance in prion research'
The work marks “a renaissance in prion research,” said Dr. Stanley Prusiner of the University of California, San Francisco, who won a Nobel Prize for discovering prions and whose laboratory developed the synthetic version. “It opens huge new vistas that were previously inaccessible,” he said.
Related diseases — including mad cow, scrapie in sheep and the human Creutzfeldt-Jakob disease, or CJD — are believed to arise when a protein the body normally harbors folds into an abnormal shape, called a prion, and sets off a chain reaction of misfolds that eventually leaves clumps of dead brain cells.
But skeptics have long questioned if these bad proteins truly act alone. Unlike viruses or bacteria, prions contain no genetic material, once thought crucial to cause infection. Repeated attempts at definitive proof of prion infectiousness have failed.
Manmade prion proves infectious
Now, UCSF neurologist Giuseppe Legname and colleagues report in the journal Science that they created a manmade prion, free of any brain tissue, that proved infectious.
They grew fragments of harmless normal protein in bacteria, purified them and flattened them into the abnormal prion shape. Then they injected the substance into brains of seven mice. It took over a year, but eventually all got sick.
The research “validates this biological process for which (Prusiner) got the Nobel Prize,” said Dr. Andrew Monjan, neurobiology chief at the National Institute on Aging, which funded the work.
“It’s terrific” work, added Dr. Richard T. Johnson, a Johns Hopkins University neurobiologist. “We kept saying, ’Synthesize one, that’s the ultimate test.’ This looks like it worked.”
Critics, however, are raising complaints. Among their concerns are that laboratory contamination with another prion strain may have sickened the animals, and that the synthetic protein was tested in genetically engineered mice that may have been particularly prone to illness.
“I don’t think it’s a proven thing. I don’t think this paper is clean,” said Dr. Laura Manuelidis, a Yale University neuropathologist. “If something is really there in science, it is there in a major way, it’s not something you have to coax out of hiding.”
Genetically engineered mice show signs of mad cow-like illnesses earlier in life than regular mice, Legname responded, but he plans to test them, too.
If the research holds up, the ability to work with synthetic prions in test tubes could help scientists develop early tests to diagnose mad cow-like diseases.
Moreover, such research also may finally reveal how the protein morphs from normal to killer and thus shed light on the human illness called “classic CJD,” Johnson said.
Mad cow disease makes headlines because eating tainted beef is linked to 150 human illnesses worldwide, most in Britain, of what’s been named “variant CJD.” But 250 Americans alone each year get the classic illness, which sometimes is inherited or caught from tainted medical equipment, but usually arises for no known reason, to families’ unbelieving despair.