- Research by North Carolina State University scientists,
in conjunction with scientists from the Netherlands and BioResource International,
an NC State spin-off biotechnology company, has shown that, under proper
conditions, an enzyme can fully degrade the prion ö or protein particle
ö believed to be responsible for mad cow disease and other related
animal and human diseases. These transmissible prions - believed to be
the cause of bovine spongiform encephalopathy (BSE), the technical name
for mad cow disease, as well as the human and sheep versions, called Creutzfeldt-Jakob
disease and scrapie, respectively - are highly resistant to degradation,
says Dr. Jason Shih, professor of biotechnology and poultry science at
NC State. But the new research, which tested the effects of a bacterial
enzyme keratinase on brain tissues from cows with BSE and sheep with scrapie,
showed that, when the tissue was pretreated and in the presence of a detergent,
the enzyme fully degraded the prion, rendering it undetectable.
- The research was published in the Dec. 1 edition of The
Journal of Infectious Diseases.
- Shih's colleagues in the research study included first
author Jan Langeveld, Dick Van de Wiel, Jan Garssen and Alex Bossers from
the Central Institute for Animal Disease Control in Lelystad, The Netherlands;
and Giles Shih and Jeng-Jie Wang from BioResource International, which
is located on NC State's Centennial Campus.
- The researchers now plan another study to test the effectiveness
of the enzyme on the treated BSE prions in mice. The two-year study begins
in January 2004 and is funded with $190,000 from the National Cattleman's
- "Our work has been done in vitro, or in test tubes,
and we've reduced the prion to undetectable levels," Jason Shih says.
"Our work with mice will show whether these undetectable levels of
prion are indeed non-infectious."
- Jason Shih will also test keratinase's effectiveness
in decontaminating equipment that processes animal by-products. Many scientists
believe that mad cow disease is spread by healthy animals eating feed containing
by-products from BSE-infected animals. Using keratinase to gobble up harmful
prions on the processing equipment would go a long way in reducing the
risk of spreading BSEs like mad cow disease, Shih believes.
- This study to optimize the degradation process is funded
for two years with $180,000 from the Food and Drug Administration. Shih
says in lieu of using actual BSE materials, which are quite dangerous to
work with, researchers will use a surrogate protein produced from yeast
that has similar physical and chemical properties, but is non-pathogenic.
- Shih hit upon the idea of using keratinase to degrade
prions based on his more than two decades of work as a poultry scientist
looking for ways to manage poultry waste. He discovered that a bacteria,
Bacillus licheniformis strain PWD-1, could degrade chicken feathers. Shih
isolated and characterized the bacterial enzyme keratinase, and then isolated
and sequenced the gene that encodes keratinase. By fermentation technology,
he was able to develop a way to produce mass quantities of the enzyme,
and did studies that proved many valuable applications of the enzyme.
- Shih found that keratinase can be added to chicken feed
to increase digestibility and the efficiency of the feed; that is, chickens
who eat feed with the enzyme grow to optimal weight quicker and need less
feed to grow to that optimal weight. The enzyme thus can provide the same
benefit in feed that antibiotics currently provide. Animal producers are
looking for safer substitutes to antibiotics, and Shih believes that keratinase
can serve that purpose.
- Soon, it will become clear whether keratinase can also
help prevent mad cow and other harmful diseases caused by prions.