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The prion hypothesis remains controversial even now, almost ten years after earning discoverer Stanley Prusiner the Nobel Prize in Medicine. The idea of an infectious protein that is capable of propagating its own misfolding to trigger the formation of proteinaceous plaques and neurological disease runs athwart much of the conventional wisdom of infectious disease research, and although much evidence has accrued to support this hypothesis, scientists on both sides continue to search for data that could conclusively prove or disprove the prion hypothesis.

One supporter of the hypothesis, Claudio Soto, has dedicated much effort to the study of scrapie, an animal disease linked to misfolded prion protein (PrP). In 2001, Soto's group described the development of the 'protein misfolding cyclical amplification' (PMCA) assay, in which brain tissue from scrapie-infected hamsters is incubated with uninfected brain tissue, triggering the misfolding of native PrP, after which the sample is disrupted by sonication and rediluted into normal brain tissue for further amplification of PrP misfolding (Saborio et al., 2001).

Now, Soto and his colleagues at the University of Texas Medical Branch describe the optimization of PMCA (Castilla et al., 2005), rapidly performing numerous rounds of scrapie PrP amplification to an extent that they are eventually left with purely in vitro–generated misfolded protein. This amplified protein not only has the same biochemical properties as misfolded PrP in samples from scrapie-infected hamsters, but is also infectious and capable of efficiently inducing scrapie in hamsters that is indistinguishable from the natural disease.

Soto sees potential for PMCA as a sensitive tool for clinical detection of the presence of misfolded prion protein. “This is a cyclical process,” explains Soto, “and you can do as many cycles as you want, depending on how much you need to amplify the signal in order to see it. In a way, it's very similar to PCR.”

He also feels that his group's findings lend strong support for the prion hypothesis. He acknowledges that not all prion skeptics will be converted: “Some people... I don't believe they will be convinced by anything.” But, he adds, “if you want to blame something to be the infectious agent behind [a] disease,” says Soto, “the best way to do that is to isolate the infectious agent, cultivate it in vitro, and show that this... will maintain and produce infectivity in a live animal—and this is exactly what we have done here.”