BioEd Online

The protein particles that cause illnesses such as mad cow disease can be found in the urine of infected mice, researchers report.

Their study may solve the mystery of how such 'prion' diseases spread among animals such as sheep, elk and deer. But it also raises concerns that the urine of humans with variant Creutzfeldt-Jakob disease (vCJD) may contain dangerous proteins.

Prions are primarily found in the brain, the spinal cord and the immune system. British cows are thought to have developed the prion disease bovine spongiform encephalopathy (BSE) by eating ground-up brains, spleens and similar material. Other body parts were thought to be relatively safe for consumption.

Then, in 2003, Adriano Aguzzi's group at the University Hospital of Zurich, Switzerland, found prions in the muscle tissue of people who had died from a brain wasting disease. And this January, the team showed in mice that prions also spread to the pancreas, kidneys and liver if there is inflammation in these organs. Together, these findings suggested that the brain and lymphatic organs might not be the only dangerous ones.

Now, Aguzzi and his colleagues have raised further concerns in a paper in Science¹.

Protein injection

The researchers took mice with a chronic inflammation of the kidney and infected them with prions. They then concentrated the proteins in their urine tenfold and injected the mixture into the brains of healthy mice. This treatment made the mice sick.

"We knew that we had something really exciting on our hands," Aguzzi says. "I couldn't believe it."

An injection of concentrated proteins from one millilitre of urine caused prion disease in half of the treated mice, Aguzzi says.

The research may explain how animals such as sheep, elk and deer transmit prion diseases. In the United States, a chronic wasting disease is spreading "like wildfire" among elk and deer, says Aguzzi. About 20% of the wild deer in some parts of Colorado are infected, says Aguzzi, and yet these animals are herbivores.

"Nobody understands what controls the spread," says Aguzzi. Dust mites have been suggested as one method of transmission. Aguzzi adds that animals may be eating urine-contaminated grass.

Low doses

An explanation that involves urine has difficulties however. The concentration of prions found in the mouse urine in the experiment was 10,000 times lower than in the lymphatic organs, and a million times less than in the brains, the original site of infection.

Neil Cashman, a prion researcher at the University of British Columbia in Vancouver, says that the risk of getting sick by touching or ingesting infected urine is minuscule. He explains that, quite apart from the low concentration of prions in urine, it would take a higher dose of the proteins to cause infection this way than through injection into the brain.

As yet, there are no data on the risk that might be attached to contact with urine from vCJD patients. On the other hand, says Cashman, "nobody wants human prions in the hospital laundry".