Researchers think they’ve solved one of the most enduring mysteries of a strange, always-fatal disease that turns both people and cows mad. In experiments with genetically manipulated mice, they found direct evidence that mad cow disease—a condition caused by a zombie-like, brain-destroying protein called a prion—can be caused by contact with sheep infected with a similar disease.
Prions are some of the weirdest things capable of making us sick. They’re proteins found in the brains and bodies of many mammal (and fungal) species that may or may not have a useful function normally. But they also can shift into a misfolded form that converts other normal proteins of its kind, much like a zombie outbreak or a toppled row of dominos. This chain reaction often takes years if not decades to kill off enough brain cells to be harmful, but once symptoms of dementia, trouble walking, or vision loss show up, death soon follows.
The first known prion disease was found in sheep as far back as the 16th century (though no one knew about prions back then). It was dubbed scrapie, after the characteristic, manic scratching of their fleece that many sheep victims displayed. In the 1980s and 1990s, we also discovered that cattle can have their own version of prion disease, formally called bovine spongiform encephalopathy (BSE), when they began dying en masse in certain countries. A few years later, it became apparent that some humans developed a new type of prion disease from eating these BSE-infected cattle.
Eventually, the mad cow outbreak was traced to cows eating feed that had been made with the brainy leftovers of other livestock, including sheep and cows—a practice now banned worldwide. Though cases of mad cow still sporadically show up, there’s never been no major outbreak on that scale since.
Some experts have speculated that the scrapie prion crossed the species barrier to cows (and from there, the BSE prion to people), sparking the outbreak. But there’s never been conclusive proof of that happening. The government of the UK, where the majority of cow and human cases occurred, concluded in a 2000 report that the 1980s outbreak was caused by cows eating BSE-infected cows, not transmission of scrapie. At the same time, they left open the possibility that the very first cases of BSE could have arisen from cross-species transmission.
In a new study published this week in the journal PNAS, scientists from the UK, Spain, France, and Portugal seem to provide concrete evidence of that transmission at least being possible.
They created mice bred to have normal prions identical to those found in cattle. Then they infected these cow-like mice with samples of the disease-causing scrapie prion—taken from sick sheep in five countries. The mice soon had detectable levels of the BSE-specific prion, suggesting an infection had taken hold. Even stranger is that when they studied the scrapie samples, they also found low levels of the BSE prion alongside the scrapie prion. Mice bred to have sheep-like prions that were then infected with scrapie also developed BSE prions alongside scrapie prions.
What this could mean, the authors said, is that scrapie isn’t really capable of spreading to cattle, per se. Rather, sheep that have scrapie also generate another kind of prion that can be infectious if it ever ends up in cattle. Either way, though, it’s the strongest evidence yet that mad cows can come from mad sheep.
“For the first time, these data bring an experimentally underpinned explanation to the appearance” of mad cow during the 1980s, study author Olivier Andreoletti, a researcher with the French National Institute for Agronomic Research, told the AFP.
There are still many mysteries surrounding prions, even if Andreoletti and his team’s work goes on to be confirmed by other scientists.
Despite millions of infected cattle thought to have entered the global food supply during the 1980s and 1990s, for instance, less than 250 people worldwide have been diagnosed with the human version of mad cow, a form of Creutzfeldt-Jakob disease. It’s likely that people’s genetics play a big part in whether the disease occurs. Another lingering question is whether eating other animals, such as squirrels and deer, can cause prion disease. Though these diseases are rare, they’re universally fatal, and for some people with very unlucky genetics, they’re inevitable. Treatment and prevention options are still much needed.
If nothing else, Andreoletti said, the findings demonstrate the importance of staying vigilant against mad cow showing up again, by maintaining the feeding and slaughter practices that stopped the outbreak decades ago.
“These measures are still in place—but they are very expensive, leading in some quarters to calls for their elimination,” he said.