Sunday, August 01, 2004

Prions and the Windows monoculture debate. My friend Keith recently sent me an email with the subject Self Organizing containing a link to the following New York Times article  Scientists are reporting that, for the first time, they have made an artificial prion, or misfolded protein, that can, by itself, produce a deadly infectious disease in mice and may help explain the roots of mad cow disease." The findings, being reported today in the journal Science, are strong evidence for the "protein-only hypothesis," the controversial idea that a protein, acting alone without the help of DNA or RNA, a cousin of DNA, can cause certain kinds of infectious diseases. http://www.nytimes.com/2004/07/30/national/30protein.html?hp I wonder if the Science article mentions the concept of enzyme in discussing prions. Prions (technically PrP-sc prions) strike me as being protein catalysts (enzymes) since they shape a chemical reaction (formation of a new protein) without being consumed by the reaction. In fact, they seem to be a unique form of self-transforming enzyme. A prion doesn't replicate (compose copies of itself from parts), it transforms the shape of an already existing (normal) prion (PrP-c) in a new (abnormal) prion (PrP-sc). This new shape can then reshape other normal proteins until all of them have been reshaped. This ability to transform from whole vs. assemble from parts is why a prion, unlike all other infectious agents, does not need genetic material. I think of a prion as an autocatalytic enzyme, self-catalyzing enzyme, or self-copying enzyme. This leads me to think of my blog entry on standards as templates. If the template has a flaw, it can prove catastrophic after millions of copies have been made from the template. Which reminds me of an email debate on the Microsoft monoculture I intended to blog but never did. Here is an excerpt that summarizes my opinion: I've resisted the urge to jump into this fray up til now because I think the issues around monoculture vs. biodiversity are so hotly debated and politically loaded in the life sciences, why would we look to them to gain insight into technological diversity? For example, if monoculture is such a bad thing, then life on earth is in trouble, because we are all based on the same set of four DNA nucleotide bases (A, G, C, T)! And ohmygod, we're all based on the same 64 codons of the "genetic code" that maps DNA to amino acids. If any hostile entity were able to inflict damage due to this fundamental "DNA monoculture" shared by all life on earth could be used to devastate the planet! Nooooo! If only evolution had been wiser and had evolved life on earth with diverse genetic architectures based on different nucleotides or different codons, we'd be at less risk out complete annihilation from one threat. I'm NOT saying diversity provides or doesn't provide benefits, inherent or otherwise. I simply point out that it is an open and interesting research question in the life sciences as to the benefits of varying degrees of biological diversity. At certain layers of the ecosystem we see massive diversity (orchids, insects), at other layers, none at all (all life uses the same four nucleotide bases; homo sapien is the only extant species descended from homo habilias-sp?), at others we see something in between (typically there are fewer "top predator" species than prey species in an ecosystem). I have my own pet theory about some of the factors that appear to govern diversity (e.g., when one layer spans another, diversity decreases in the spanned layer, and increases in the layer above the spanning layer), which I'll write down one of these days. Bottom Line: No one knows the general laws of equilibrium or optimization of diversity vs. homogeneity in biological ecosystems, so why go around spouting dubious monoculture analogies to software ecosystems. Talk about useless FUD. It now strikes me that the existence of deadly prions is a perfect biological analogy to the Windows monoculture risk. Just as the whole world is at risk from a single Windows virus because we all use Windows, we are all at risk from a single prion (PrP-sc) because we all use the same protein shape in our brains. Is having massive numbers of identical PrP-c's (ie, a prion monoculture) in our brains good or bad? Its good because it makes the brain possible, its bad because it makes it vulnerable. 5:10:08 AM