Nancy H. Ruddle, Ph.D. ’68, the John Rodman Paul Professor of Epidemiology and Public Health and professor of immunobiology, is the first to admit that she’s no expert on mad cows. Her laboratory studies the human lymphoid system and how it mediates chronic infection and autoimmune diseases such as diabetes and multiple sclerosis. But Ruddle’s recent collaboration with pathologist Adriano Aguzzi, M.D., Ph.D., in Switzerland has overturned one of the major tenets of public health efforts to curb mad cow disease.
More formally known as bovine spongiform encephalopathy (BSE), mad cow disease is caused by prions—misfolded protein fragments that clump together and destroy the brain. Other animals, such as sheep, goats and mink, are also susceptible to prion diseases. In fact, researchers believe that the mad cow epidemic started because animal feed was contaminated with the brains of sheep infected with the prion disease scrapie. In humans, contraction of the variant Creutzfeldt-Jakob Disease has been attributed to eating BSE-infected beef—specifically, the animals’ brain, spinal cord and immune system tissues such as the spleen and lymph nodes. Experts have assumed that other parts of the animal were safe to eat.
Aguzzi, a professor of neuropathology and molecular biology at the University of Zurich, has long been on the trail of prion diseases. In 1997 his team showed that the immune system’s B cells, or B lymphocytes, which are activated when the body mounts an immune response against common infections, may cause prions to replicate and spread. But no one knew how far.
Ruddle’s team was working with mouse models of inflammation in the kidneys, pancreas and liver. Her work had shown that in chronic immune diseases, T and B cells can form outposts outside of the immune system that are very similar to lymph nodes. Since prion levels are known to be high in lymph nodes, the international team hypothesized that the organized outposts may allow spread of prions to other organs of the body beyond the nervous and immune systems. Sure enough, the researchers reported in January in the journal Science that when Ruddle’s mice were infected with prions, their inflamed kidneys, pancreases and livers carried enormous prion levels—as high as those found in diseased spleens.
“It was thought that even if a cow was infected (with BSE), what was most important was that the brain didn’t get into the feed. But if you have a chronic infection in that animal, you need to think about that, too,” Ruddle said. The work may have far-reaching implications, such as the need for increased monitoring of farm animals, says Ruddle. Although cattle are routinely checked for fever, some inflammatory conditions such as early forms of diabetes, she notes, would not necessarily have visible symptoms.