July, 2004- Mad-cow disease and a handful of other vexing neurological disorders are known to be caused by prions or infectious proteins. However, the question of whether or not proteins by themselves can be infectious (the protein-only hypothesis) has been controversial since the hypothesis was first proposed. In an important new paper Dr. Ilia Baskakov of the Medical Biotechnology Center and his co-workers at the University of California San Francisco have made a significant breakthrough. They have finally done what skeptics in the field have said must be done in order to substantiate the hypothesis: the final proof of the protein-only hypothesis will require the engineering in vitro of a synthetic infectious protein capable of propagating a prion in vivo. (1). In a report in Science published on July 30, 2004 (2), they have presented the first evidence that a synthetic protein can be infectious in vivo.

Figure 1: Amyloid fibrils produced using Dr. Baskakov's cell free conversion technique.

Using the protocol that Dr. Baskakov developed for the cell free conversion of recombinant PrP into infectious amyloid fibrils (3), a critical first step in the process, they injected the synthetic, infectious fibrils into transgenic mice. These mice developed neurological symptoms. Brain extracts from these mice were then injected into normal mice, which subsequently showed the same symptoms, demonstrating the infectious nature of the artificially created prion.

Before joining the MBC faculty, Dr. Baskakov was a postdoctoral fellow with Dr. Stanley Prusiner's, who won the 1997 Nobel Prize in Medicine for his discovery of prions. Dr. Baskakov noted that creation of a synthetic infectious prion is is an essential step forward toward understanding the chemical nature of the infectious agent of mad-cow disease and other prion maladies. He has established his own prion research group which is at the forefront of prion research. He continues to develop in vitro methods for the production and detection of prions and for examining the biophysical properties of prion proteins.

(1) Soto, C. & Castilla, J., The Controversial Protein-Only Hypothesis of Prion Propagation, Nature Medicine Online, pp S63-S67, July 2004.
(2) Legname, G., Baskakov, I.V., Nguyen, H.O.B., Riesner, D., Cohen, F.E., DeArmond, S.J., Prusiner, S.B. 2004. Synthetic Mammalian Prions. Science 305:673-676.
(3) Baskakov, I.V., Legname, G. , Baldwin, M.A., Prusiner, S.B., Cohen, F.E. 2002. Pathway Complexity of Prion Protein Assembly into Amyloid. Journal of Biological Chemistry 277:21140-21148.