or poultry science researcher Jason Shih, December was a month of coincidence: The first U.S. case of madcow disease was reported, just as Shih published a paper in a national journal describing the discovery of an enzyme that could destroy the prion – or protein particle — that causes the disease.
The paper, published in the Dec. 1 issue of The Journal of Infectious Diseases, described Shih’s finding that the enzyme keratinase could fully degrade the prion that causes mad cow disease. On Dec. 23, the U.S. Department of Agriculture announced the first U.S. case of mad cow disease, also known as bovine spongiform encephalopathy (BSE). An adult Holstein cow in Washington state, imported from Canada, tested positive for the disease.
In the mid-1990s, scientists discovered a link between BSE in cattle and a degenerative human disease, variant Creutzfeldt-Jakob disease. Both diseases are similar to a sheep disease called scrapie.
Humans can become infected by eating beef contaminated with brain and spinal cord tissues of BSE-infected cows. Until December, the United States had successfully held off the disease, which has plagued Europe for 20 years. In Europe, the spread of BSE was linked to the practice of feeding beef by-products to other cows, a practice prohibited in the U.S.
Shih’s findings regarding keratinase and BSE resulted from his research seeking new ways to degrade poultry waste, particularly feathers. For many years, he has studied how keratinase, a protein produced by the bacteria Bacillus licheniformis strain PWD-1, can be used to break down the hard protein in poultry feathers.
In addition, keratinase proved to be an effective poultry feed additive, helping birds to more efficiently utilize nutrients. Growers could benefit from using the enzyme to grow bigger birds with the same amount of feed. Keratinase could replace antibiotic growth regulators that are being phased out.
Two years ago, Shih discovered that the structure of the prion that causes BSE is similar to that of chicken feathers. He turned to a skeptical colleague at the Central Institute for Animal Disease Control in The Netherlands, to help test his theory that keratinase could break down BSE prions, just as it breaks down poultry feathers. Research using BSE-infected materials is very risky and is not permitted in the U.S.
The Dutch researchers found that under special circumstances, keratinase completely degraded the BSE prion. The news came as a surprise to the researchers, Shih said, because the prion in its pathogenic form is very stable and hard to destroy through normal processes. Disposal of infected animals and tissues is difficult and expensive, he said.
Shih has received a $190,000 grant from the National Cattleman’s Beef Association to continue the collaboration with his Dutch colleagues, investigating how keratinase degrades the BSE prion. This time, they want to test the effectiveness of the enzyme on BSE prions in mice. Researchers want to confirm that the pathogenic prions are indeed neutralized by keratinase.
In related research, U.S. scientists are studying a yeast protein with a structure similar to the BSE prion to determine if keratinase can destroy pathogenic BSE prions. This study is funded by a $180,000 grant from the U.S. Food and Drug Administration. The research is being conducted in collaboration with BioResource International (BRI), an N.C. State spinoff biotechnology company.
If keratinase is proven effective as a cleaning agent, the enzyme would be useful in several ways, Shih said. Currently, BSE-infected material must be burned or treated with highly caustic chemicals. Keratinase could be used for cleaning meat-processing equipment exposed to an infected animal, for disposing of infected tissues or for decontaminating hospital equipment exposed to patients with variant Creutzfeldt-Jakob disease.
“We’re really excited about this opportunity,” said Giles Shih, president of BioResource International and Jason Shih’s son. “This is an idea that has gone from the lab bench to applications in the field.”
Giles Shih said BRI is working closely with USDA to develop new ways to prevent the spread of BSE, including disinfection and detection. Under current USDA standards, about one in 2,000 beef cattle slaughtered are tested for BSE, but Japan is requiring all animals to be tested before the country will accept U.S. beef for import. Developing a rapid test for detecting BSE is another food safety measure BRI is investigating, he said.
“We need some better preventive measures for this disease, although we have held it off for 20 years,” Jason Shih said.