THE CONTROVERSY BEHIND PRIONS

Ever since Stanley Prusiner coined the term prion in 1982 and showed that purified prions can transmit spongiform disease, skeptics have been trying to prove him wrong. The idea that a protein can reproduce itself without going through a nucleic acid intermediate goes against everything we know about transmissible diseases. Even the simplest viruses contain genetic material, DNA or RNA, that codes for proteins necessary for function and transmission. Because prions appear to be infectious proteins that can self-replicate, the central dogma of molecular biology, (DNA to RNA to protein) seems not to apply here. So maybe these scientists are right to be skeptical. To the right are some of the reservations skeptics have about the protein-only hypothesis.

• The strain phenomenon

Scrapie and other spongiform diseases come in distinct strains that differ in their incubation period, symptoms, and effects on different brain regions. Skeptics argue that these differences are due to mutations in nucleic acid and is evidence that prions do indeed have genetic material.

• Information from other amyloid diseases

Alzheimer's disease, Parkinson's disease and Huntington's disease are also characterized by the formation of misfolded protein into amyloid fibers, resulting in neurodegeneration. But these diseases are not infectious, leading to the argument that misfolded protein alone is not enough to transmit disease.

• Answering the skeptics

The ultimate test of the protein-only hypothesis would be to produce PrP-res in a test tube, inject it into a normal healthy brain, and show that spongiform disease results. In April 2005, scientists at the University of Texas performed this experiment successfully showing that PrP-res is indeed infectious. Questions still remain about what exactly triggers the folding of PrP-sen into PrP-res.