A team of scientists led by biotech pioneer Leroy Hood have spotted a set of genes that go haywire in mice infected with a form of “Mad Cow” disease—a finding that could pave the way for more effective early diagnostic tests for the brain-wasting condition in cattle.
The new findings are being published online today in Molecular Systems Biology, a journal from the Nature Publishing Group. Hood told me yesterday this is one of his most significant scientific publications in years, and it is being hailed in an accompanying review article as a “landmark” in the field of systems biology by Gilbert Omenn, the director of the University of Michigan’s center for computational medicine and biology. The field of systems biology seeks to use high-powered computers to analyze the whole biological system, rather than the traditional approach of isolating one gene or protein to study at a time.
“We were able to see genes perturbed 8 to 10 weeks before any symptoms were observed,” Hood says. “This could be used for presymptomatic diagnosis.”
This disease made headlines around the world in the early 2000s, particularly in the United Kingdom. The condition in cattle, known as bovine spongiform encephalopathy, is thought to be caused by a misfolded protein called a prion. The disease created some amount of hysteria in the past, because it is thought that humans can develop a variation called Creutzfeldt-Jakob disease by eating diseased material from the brain or spinal cord of infected cattle. The disease is extremely rare in people—with 165 documented cases in the UK through February—according to the University of Edinburgh. It may not be a huge cause of death in people, but it was scary enough to cause British agricultural officials to kill 4.4 million cattle in that country as a precaution, according to this 2001 story in The Telegraph of London.
Scientists at Hood’s Institute for Systems Biology in Seattle, including lead author Daehee Hwang, were joined in their analysis of the genetics of prion disease by collaborators at the McLaughlin Research Institute in Great Falls, MT, the University of California, San Francisco, the Allen Brain Institute in Seattle, the I-Bio Program at Postech in Korea, and the European Bioinformatics Institute in Cambridge, UK.
The researchers took 30 million measurements from the brains of the infected mice and used high-powered statistical and computer models to separate signal from noise, Hood says. They were able to narrow it down to 7,400 genes—about one-third of the mouse genome—that were affected by the misfolded prions, which researchers again were able to narrow down to 333 “core” genes that were perturbed, Hood says. Researchers looked at the genes at 10 different time points, and noted which genes were altered for weeks before symptoms showed up. Some of these genes make proteins that are secreted into the blood, which could make for a relatively practical new diagnostic test, Hood says.
There’s currently no cure for prion disease in people, and the U.S. Department of Agriculture may or may not be interested in getting a test, Hood says, but agricultural officials in Japan and Korea would certainly like to have such a test to check on the health of their cattle herds. Since networks of genes are perturbed by prion infections, it’s also possible this condition may lend itself to treatment with microRNA drugs that are still in “very early” stages of development, Hood says.
Even more importantly, this study of systems study of how genes react when exposed to an infectious invader could hold implications for the study of HIV, tuberculosis, malaria, and all sorts of other bugs that kill a lot more people than “Mad Cow” disease ever will.
