northanger (northanger) wrote,
northanger
northanger

Triangulating Prions

thanks again to DarkSyde: two new Lemur species @ science blogger Afarensis (see: Australopithecus afarensis, aka "Lucy") — good quotes, good stuff & a good science news feed - "The Prion Anomaly" caught my eye. reading about PRION wondered if it was related in any way to H5N1 & found more interesting links at Above Top Secret News Network: Tamiflu & cyclones. just in case you don't go past the fold, think this comment extremely relevant: "The way I have come to see what's happening is this - We have changed our environment - substantially, chemically, and biologically - and now it's changing us - something that is necessary for our survival. We are part of the environment - a component and inextricable part of the larger system - and need to be in harmony it. Microbes (and prions) are the 'mediators' between complex life and the environment, or larger system. So-called 'disease' is simply transition, painful as it may be."

UPDATE :: after digesting this (no pun, honest), think key point from tamiflu article mentioned above is this: There has been human-to-human transmission. What everybody is watching for is SUSTAINED human-to-human transmission. And in Viet Nam/Cambodia, there have been "clusters" of infections that would indicate a sustained human-to-human transmission. But it hasn't been confirmed. see: WHO pandemic phases.

What about the pandemic risk? (WHO) A pandemic can start when three conditions have been met: a new influenza virus subtype emerges; it infects humans, causing serious illness; and it spreads easily and sustainably among humans. The H5N1 virus amply meets the first two conditions: it is a new virus for humans (H5N1 viruses have never circulated widely among people), and it has infected more than 100 humans, killing over half of them. No one will have immunity should an H5N1-like pandemic virus emerge. All prerequisites for the start of a pandemic have therefore been met save one: the establishment of efficient and sustained human-to-human transmission of the virus.

good link explaining evolving WHO verbiage:

By early 2005, these clusters account for almost one third of H5N1 cases. In Indonesia, the number of H5N1 patients in familial clusters grew to about two thirds of cases. The initial 15 clusters were described in a recent CDC/WHO publication. At that time, WHO changed wording in their characterization of the H5N1 outbreak. They had indicated that there was little evidence for human-to-human transmission. This changed to little evidence for efficient human-to-human transmission, acknowledging the growing number of familial cases which involved human-to-human transmission. Recently, the size and number of these clusters grew, and WHO again changed their description from a lack of evidence for efficient human-to-human transmission to a lack of evidence for sustained human-to-human transmission. Although this terminology suggests the increased frequency has been noted by WHO, public comments and media reports still leave the impression that human-to-human transmission of H5N1 is rare or non-existent. This impression is particularly misleading at the present time because a genetic change has been noted in H5N1 from the index case in Turkey.

Wikipedia: Prion

A prion (pronounced "PREE-on") — short for proteinaceous infectious particle — is a unique type of infectious agent, as it is made only of protein. Prions are abnormally-structured forms of a host protein, which are able to convert normal molecules of the protein into the abnormal structure. Amyloid describes various types of protein aggregations that share specific traits when examined microscopically. The name amyloid comes from the early mistaken identification of the substance as starch (amylum in Latin) Though the exact mechanisms of their actions and propagation are unknown, it is now commonly accepted that prions are responsible for a number of previously known but little-understood diseases generally classified under transmissible spongiform encephalopathy diseases (TSEs) ... So far all prions discovered are believed to infect and propagate by formation of an amyloid fold. However, since any infectious protein particle would be defined as a prion, other mechanisms may be possible ... The theory that TSEs are caused by an infectious agent made solely of protein has been around since the 1960s ... A breakthrough occurred in 1982 when researchers led by Stanley B. Prusiner of UCSF purified infectious material and confirmed that the infectious agent consisted mainly of a specific protein. Prusiner coined the word "prion" as a name for the infectious agent, by combining the first two syllables of the words "proteinaceous" and "infectious." Prusiner's intention was for the word 'prion' to be pronounced 'pree-on'. While the infectious agent was named a prion, the specific protein that the prion was composed of was named PrP, an abbreviation for "prion-related protein". Stanley Prusiner was awarded the Nobel Prize in physiology or medicine in 1997 for this research. Further research showed that PrP is found throughout the body, even in healthy people and animals. However, the PrP found in infectious material (i.e. the PrP that forms prions) has a different structure and is resistant to proteases, the enzymes in the body that can normally break down proteins.
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Prior to Prusiner's insight, all known pathogens (bacteria, viruses, etc.) contained nucleic acids that are necessary for reproduction. The prion hypothesis was highly controversial, because it seemed to contradict the "central dogma of modern biology" that asserts all living organisms use nucleic acids to reproduce. The "protein-only hypothesis" — that a protein (which, unlike DNA, has no obvious means of replication) could reproduce itself — was initially met with skepticism. However, evidence has steadily accumulated in support of this hypothesis, and it is now widely accepted. Rather than contradicting the central role of DNA, however, the prion hypothesis suggests a special case in which merely changing the shape, or conformation, of a protein (without changing its amino acid sequence) can alter its biological properties.

The Prion Anomaly

These tiny, eccentric proteins are challenging a central paradigm in molecular biology: that genes are the sole unit of inheritance.

Science has been progressing at a fantastic speed this decade. For old timers such as myself, the replacement of paradigms in biology has been intellectually bearable, but only just so. I was born and educated in the era before 1950, when life was the domain of proteins, and I had to adapt myself to a new way of looking at life after the discovery of the double helix and the nature of the genetic code. James Watson and Francis Crick’s seminal paper, in 1953, finally provided the structural and chemical explanation of how cells store, use, and pass on information to daughter cells. This gave rise to the central paradigm in molecular biology: that structural information in the cell flows irreversibly from gene to protein, intrinsic to which is the concept that the sequence of amino acids in a protein entirely governs its final structure. Similarly, what is true for protein synthesis is also true for the mechanisms of heredity: that the genome (the full complement of genes in a cell) controls phenotype (all the characteristics of a living organism).

More than a half-century later, a large majority of biologists believe that the mechanism postulated by molecular biology is not only true, but the only conceivable system in life. Yet, a small number of researchers have recently discovered provocative anomalies that are threatening this scientific idea. The question then is this: Is the central paradigm of molecular biology—that all genetic information is stored and transferred digitally through DNA—the only possible explanation of how life evolved, or are there other mechanisms of heredity in living organisms? Evidence is mounting that hereditary information can be transferred in an analogous way through the prion.

The word “prion” was coined by Stanley Prusiner at the University of California San Francisco in 1982, as an acronym for “proteinaceous infectious particles.” The term was chosen to emphasize that the infectious agent he was studying was a protein, not something “contaminated” by viral nucleic molecules, as had been suggested. For at least 25 years, scientists had suspected that strange agents, called “slow viruses,” were behind degenerative brain diseases including scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and kuru and Creutzfeld-Jakob disease (CJD) in humans, but they hadn’t been identified. Prusiner was the first to hypothesize that the causal agent common to all these diseases was a prion. The idea was received with great scepticism by the biomedical community, which demanded an explanation for how a molecule without DNA or RNA could trigger disease. But Prusiner went on to experimentally prove his theory and to discover that prions are actually just misfolded, endogenous proteins that can cause other proteins to change shape, thereby transmitting structural information from one molecule to the next.
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More recently, prions were found to have a role in another sacred domain of biology: the transfer of hereditary information in a non-Mendellian fashion from parents to offspring. It was in yeast that researchers first found evidence that prions could alter the expression of enzymes from one cell to another. Far from being pathologic, this form of protein-based information flow was an adaptive mechanism, conferring evolutionary advantages onto recipients. And recently, Susan Lindquist at the Whitehead Institute in Cambridge, MA (who has been working on prions with her group since 1993) has found a notable example: a molecular chaperone, the prion Hsp90, that strengthens the hereditary evolution of drug resistance in diverse fungi. But it is the evidence that prions play an important role in the formation and maintenance of long-term memory—discovered by Eric Kandel at Columbia University in New York—that seems to me of greatest importance.

Scientific revolutions concern the replacement of an old paradigm by a new, incommensurable one. However, the conflict of paradigms often does not end with the death of the old one. Rather, the new theory is incorporated into the older framework so as to make it more universal. Physicists have become quite used to this and have been quick to adapt their common views to new theories. But I wonder if we are not, today, in a new epistemological situation in which two apparently incompatible paradigms can exist simultaneously: in this case, the classical (molecular biology) paradigm and the prion paradigm. After all, is it not the case in physics that Albert Einstein attempted for 40 years to reconcile the relativity and quantum paradigms, with no success? {continue...} {More on Prions}

H5N1 Is Developing Tamiflu Resistant Genetic Mutations (15-Oct-2005)

A Vietamese girl who was directly infected with H5N1 from nursing her brother who was also ill from the disease, has been found to be carrying Tamiflu resistant strains of the disease. The girl was given Tamiflu as a precaution whilst caring for her brother but the medication did not stop the disease from developing. She was later given more Tamiflu as treatment and did survive. Tests have now shown she was carrying several different strains of H5N1 and that a few of those strains had developed genetic mutations which were resistant to Tamiflu ... This girl was directly infected by her brother which shows the disease must have mutated in that family for it to happen. Couple that with the Tamiflu resistant strains and it could well be a forecast and hint of things to come.

comments to this story (mostly by soficrow:

Welcome to the wonderful world of prion-related disease.

...There is much proof and little doubt that 'modern' microbes interact with medicine and drugs to create new disease strains - the pathway is via prions (of course) that respond to environmental change (like drugs in the body) by adapting, mutating into a new conformation, and thereby, creating a new strain. Point being that it's not just humans and animals that get prion diseases, but microbes too. The microbe-prion relationship originally was perceived as prions 'hitchhiking' on microbes - and that may be correct - but in fact, the relationship is more complex. In a microbe-prion relationship, when the prion mutates into a new strain, so does the microbe.

If it makes you feel any better - and it should - this all has been going on for a very long time now - and escalating dramatically over the past 3-4 years. We really are at the apex - a climax of evolutionary change. Last year - I was incensed at the obstacles and deadlocks preventing vaccine production - and at the obstacles to stem cell therapy, which I know to be very advanced. This year - I am kind of hohum. I really do believe that we're better off letting 'nature' handle it.

The way I have come to see what's happening is this - We have changed our environment - substantially, chemically, and biologically - and now it's changing us - something that is necessary for our survival. We are part of the environment - a component and inextricable part of the larger system - and need to be in harmony it. Microbes (and prions) are the 'mediators' between complex life and the environment, or larger system. So-called 'disease' is simply transition, painful as it may be.

Bird Flu, and the "Neglected Epidemic" (06-Oct-2005)

The world's leading medical journal on infectious disease, The Lancet, just released a series called "The Neglected Epidemic." The series is about chronic disease, which accounts for 52% of deaths in the world today, as well as rampant disability and debilitation. The Lancet says it is critical to intervene early in the epidemic's course, stating "There is an unusual opportunity before us to act now to prevent the needless deaths of millions." The series' lead article laments the fact that reducing chronic disease is not a Millennium Development Goal (MDG).

The Lancet series is good - as far as it goes. But it begs the issue, and does not admit outright that chronic disease is infectious, or that most chronic disease results from underlying infection with a prion called "a-smooth muscle actin" (ASMA). Instead, it echoes populist claims that chronic disease results from "lifestyle" and is a "personal responsibility." Accordingly, the series promotes educating people on the dangers of tobacco use and bad diet - towards a 2% reduction in deaths by 2015.

Granted, avoiding contaminants in water, food, and medicines is nigh impossible, while individuals do have some hope of controlling tobacco use and bad diet. And avoidance is good advice - there is no doubt that common contaminants speed progression of the underlying disease, cause mutations, and create new disease-causing prion strains. And maybe, it really is too late to clean this filthy barn we call a planet. But. Must we continue to blame the victims?

Most noticeably, The Lancet skirts the biggest health issue facing the world today:

1. Many people in the world - and almost 100% of Americans are infected with an underlying prion disease;

2. Prion diseases use the immune system to spread through the body, and progression speeds up dramatically in the presence of inflammatory illness like the flu;

3. When bird flu hits, the real problem is not the expected fatality rate, but the fact that survivors will become progressively more debilitated and disabled with chronic disease - and may live for decades as unproductive members of society.

Links :: {Prusiner Autobiography} {Protein Prion Production} {What a week for prions}

{'Between the geek and the meek' (tangents)}

The Hunger is a 1983 (R) rated horror film. It is the story of a bizarre love triangle between a doctor experimenting with aging and a stylish vampire couple, starring Catherine Deneuve, David Bowie, Susan Sarandon and Cliff DeYoung. + In this film, genetic material (similar to a virus or prion) is passed from true vampires (a different species) to create temporary vampires (a few centuries or so) from humans. The human vampires act as companions until they eventually wither. Unfortunately for the human vampires, they never die (unless burned) and remain in a conscious, desiccated state (a form of living hell). The lineage of the true vampires begins in ancient times, passes through the Egyptian dynasties, and into the present. + The film shares plot line and visual elements with other road movies, particularly the 1979 movie Messidor by Alain Tanner. Messidor was the tenth month in the French Republican Calendar. The month was named after the Latin word messis, which means harvest. Messidor was the first month of the summer quarter (mois d'été). It started June 19 or June 20. It ended July 18 or July 19. It follows the Prairial and precedes the Thermidor.

Tags: astroschyzy, darksyde, orchis, pandemic, prion
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