They are perhaps the most mysterious molecule discovered in the human body yet. Prions are the infectious agents behind “mad cow disease” or bovine spongiform encephalopathy in cows, Creutzfeldt-Jakob disease in humans, and scrapie in sheep. Scientists today face a mountain of questions about these diseases and the insidious proteins gone bad that cause them.
“In the early eighties, when [scientists] didn’t know that prions are what they are…they thought they were viruses,” explained U of T professor of virology Mounir Abouhaider.
Now, scientists know that prions are produced by the body as any other protein is, via genes. Prion diseases in livestock have been known for centuries, as had the rare cases of neurodegenerative Creutzfeldt-Jakob disease. But until two decades ago, no one suspected one of the body’s own proteins could be responsible.
“Everyone was looking for a bit of nucleic acid [because] you can’t have an infectious agent without RNA or DNA in it,” recounted Abouhaider.
The discovery in 1982 that a “proteinaceous infectious particle” could spread disease caused upheaval in the medical world.
“That was a novel thing because it was not easy to understand how a protein could be an infectious agent.”
But prions only entered the public stage when an outbreak of Creutzfeldt-Jakob in the U.K. killed 100 to 150 people in the late eighties. At that time, scientists could not conclusively pin down the source of the outbreak, contaminated beef.
Of the body, for the body?
Infectious prions are unique super-villains in the protein society of the human body. At first glance, prions seem to be nothing more than malformed, highly durable proteins that reshape regular, harmless prions into disease-causing particles simply by coming into contact with them. No other human protein can transform normal proteins like this, and no prion can resist being transformed.
Normal, healthy prions are found all over the nervous system, occurring in the highest levels in the brain. Natural prions do not cause disease, but the role they do play in our bodies is still unknown.
Researchers also don’t know what makes a prion “go bad.” In inherited prion diseases, like cases of Creutzfeldt-Jacob that can be traced in genealogies, the “bad” prion is encoded in a person’s genes. In transmitted cases, like human “mad cow” outbreaks, a malformed prion is ingested and begins its slow spread through the brain. Some cases, which don’t seem to fit either criterion, are called spontaneous.
Regardless, the disease that results is almost always the same. The years-long breakdown of brain cells impairs function after function, until not even the cells that control breathing remain functional. It’s no coincidence that bad prions cause neurodegenerative disease because most normal prions are found in the brain.
Bad prions warp healthy ones into copies of themselves by simply touching them-an idea so strange and new that some scientists don’t believe it. Abouhaider, however, is among the majority of scientists that supports the idea. He dubs the conversion of a normal prion to an infectious prion a “flip.”
“If one of them flips and it’s sitting next to its sister, which is in the proper form, it will flip [its sister] into its infectious form. You only need to have one [infectious prion] to convert the regular protein to the infectious form by touching it.”
It may take up to 30 years, but a single infectious prion in the brain will convert every normal prion until bunches of prions form larger and larger clumps. These plaques get so large and intrusive that cells begin to die.
They’re beefy little suckers, to say the least
One of the reasons infectious prions manage to survive the stomach, whose acidity can break down almost everything, is their incredibly resistant structure.
Infectious prions make use of a robust form described as beta sheets-a structure that can also be found in hair-to endure harsh conditions. Even modern sterilization techniques such as autoclaving cannot break down a prion.
“The hair is a protein and you can swallow a hair and it comes out as a hair,” described Abouhaider. “So the enzymes in the stomach can’t digest [a prion]. It has the potential to infect other [prions].”
Blood transfusions are a prion infection hazard when a blood donor doesn’t know he or she has a prion disease. The slow spread of the disease means that many remain unaware of their condition until their cognitive abilities begin to fail in the later stages of the illness.
With the addition of Creutzfeldt-Jacob cases caused by contaminated medical instruments, the death toll has risen to 160 in the U.K. But Abouhaider and other epidemiologists are confident that number won’t spike again anytime soon.
“There’s still a scare in England,” said Abouhaider. “During that outbreak of mad cow disease in England, very few right away showed the signs of the disease and died. People [thought that] by five or 10 or 15 years later, there [were] going to be a huge number of people showing the disease. But this doesn’t seem to be the case.”
