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France issues moratorium on prion research after fatal brain disease strikes

sciencemag.org

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Re: France issues moratorium on prion research after fatal brain disease strikes

#231
post #34

Earlier quoted context omitted.

What's "effective" mean in this context? The anthrax letters in the US in 2001 certainly dominated news cycles.

The most effective bioterror attack in the USA was https://en.wikipedia.org/wiki/1984_Rajneeshee_bioterror_atta... and it killed zero people, affecting 751 people in total. Bioterror is expensive and difficult. For prions specifically, the main "problem" (which is a good thing overall for us) is that they're naked proteins, and they denature relatively quickly when outside of a protective environment. Spray them onto…

> For prions specifically, the main "problem" (which is a good thing overall for us) is that they're naked proteins, and they denature relatively quickly when outside of a protective environment.

How does this jive with the seemingly extreme difficulty of effective sterilization of prion-contaminated objects?

https://academic.oup.com/cid/article/32/9/1348/291736

Re: France issues moratorium on prion research after fatal brain disease strikes

#232

Earlier quoted context omitted.

I just wanted to add a comment about your muscle bulk comment. Protein in protein shakes is usually denatured or rather just a collection of amino acids. Proteins that are synthesized by the body have a structure to them and Prions are simply misfolded representations of those proteins. The process of destroying a Prion involves denaturing it by removing its structure. I don't believe that muscle tissue is anymore re…

Just for clarity - my last line there was me being facetious! I was under the impression that even boiling or bleaching did little to kill prions? I seem to recall that even autoclaving surgey equipment did nothing to them, so they had to be thrown? Otherwise, yes - there're lands of opportunity in the science of protein un/folding.. but as much, there's scope for naughtiness too. Seems to me like this level of tech…

Ah apologies. And Bleach is utilized in the labs to denature the prions appropriately. You're correct that autoclaves are not used as heat unfortunately is not enough to kill them.

Its like 100% bleach.

Re: France issues moratorium on prion research after fatal brain disease strikes

#233
post #37

From Wikipedia [1]: « Prions are misfolded proteins with the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several atal and transmissible neuro degenerative diseases in humans and many other animals. It is not known what causes the normal protein to misfold, but the abnormal three-dimensional structure is suspected of conferring infectious properties, collapsing…

Well we don't really know that, because diagnosis is normally confirmed post-mortem. There could be many people walking around infected with prions that show no symptoms at all.

There's some pedantry here.

There is evidence that some people have a mutation that prevents them from getting CJD. The mutation causes a small change in the proteins that CJD prions impact (changing a glycine to valine at a certain part of the protein). The working theory is that that structural change prevents CJD prions from being able to re-form healthy proteins, preventing the spread of the disease. I wouldn't be at all surprised if those proteins are eventually broken down by the body and removed.

All that being said, I don't know if you would even consider it an "infection" if the person is immune to the prions spreading. Prions aren't generally transmissible, so if the prions don't do anything and can't be transmitted... is anything actually wrong? You and I are exposed to tons of bacteria every day, but as long as your body can fight it off (i.e. no symptoms and no transmission), we wouldn't usually call that an "infection". In the same light, presence of abnormal proteins that aren't causing an issue doesn't seem like something we would call an "infection".

There's also the fact that some people inherit the disease (as in their body actually makes the prions itself), which doesn't make any sense in the context of an "infection". It's their own body producing the prions, so in those cases it's a genetic disease, not an infection.

Re: France issues moratorium on prion research after fatal brain disease strikes

#234
post #31

Hm: "long period of uncertainty began on 31 May 2010, when she stabbed her left thumb with a curved forceps while cleaning a cryostat—a machine that can cut tissues at very low temperatures—that she used to slice brain sections from transgenic mice infected with a sheep-adapted form of BSE . She pierced two layers of latex gloves and drew blood" Later in the article: ""We conduct research only on mouse-adapted sheep…

"infect" is not the right word. Prions are not viruses, they do not replicate, they ravage other proteins in their surroundings by misfolding them over and over again until it becomes a fatal pathology.

Prions are considered infectious, although when they were first proposed it was essentially heresy that something could be infectious without containing any nucleic acid (DNA/RNA).

Whether they self-replicate or not is sort of a semantic issue. They replicate in the same way "fallen-down dominos" replicate.

Prior to being a prion, they are an already complex protein, but by folding a particular way, they become a prion, which causes other proteins of the same type to fold similarly.

Re: France issues moratorium on prion research after fatal brain disease strikes

#236

Hm: "long period of uncertainty began on 31 May 2010, when she stabbed her left thumb with a curved forceps while cleaning a cryostat—a machine that can cut tissues at very low temperatures—that she used to slice brain sections from transgenic mice infected with a sheep-adapted form of BSE . She pierced two layers of latex gloves and drew blood" Later in the article: ""We conduct research only on mouse-adapted sheep…

Also I would be fine with studying prions in general. But I don’t think creating new ones is such a great idea.

Re: France issues moratorium on prion research after fatal brain disease strikes

#237

Earlier quoted context omitted.

It's not really effective because it takes years to manifest symptoms of prion disease. Terrorism usually has a message attached to it, and "you're gonna start dying in 10 years" is not conducive to messaging.

In this case I guess the message targets people in other cities than the doomed one. "This could happen to your city too".

Wouldn't an entire city being sprayed with prions be a fairly apocalyptic event in and of itself? Those prions aren't going to go away, they'll get blown about and distributed by the millions of cars, buses, and trains going in and out of the city. What can you realistically do about that, go full Imperial Inquisition and raze the entire section of the country to the ground?

Re: France issues moratorium on prion research after fatal brain disease strikes

#238
post #56

Prions are weird. I was at UCSF during the time they went from a fringe theory to an established fact and a nobel prize. The professor who studied them (Prusiner) had to overcome tons of resistance and the experiments were heroic (often waiting months for mice to die). It's really funny that everybody resisted it until somebody mentioned that there was a plausible physical mechanism of refolding catalysis.

Is it because many researchers put their ego first over the science? It's so many times that they ridicule ideas, that often amounts to bullying and then they rarely even say sorry when it turns out they were wrong. Why won't academia flush out these types of people? The toxic atmosphere with no way of getting rid of bad apples is what put me off from studying.

This phenomenon is studied in the history and philosophy of sciences; it is called "paradigm change" ala Thomas Kuhn. Yes, researchers who work in the dominant 'paradigm' tie their psychological identities with the paradigm they are working on. So, this resistance is expected.

'How to overcome resistance' is studied in Sociology of Science.

Re: France issues moratorium on prion research after fatal brain disease strikes

#239

Earlier quoted context omitted.

This article from 2011 suggests aerosol transmission in mice: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020930/

To attenuate fears a bit... Aerosol transmission was proven possible if you're sitting inside a vapor inhalation chamber equipped with a nebulizer spraying out liquid droplets containing >2% w/v brain homogenates from terminally scrapie-sick mice. Rest assured if you somehow get infected by PrPSc through airborne transmission, someone was trying really hard to make that happen.

>a vapor inhalation chamber equipped with a nebulizer spraying out liquid droplets containing >2% w/v brain homogenates from terminally scrapie-sick mice

I have never been more grateful to be a backend web developer where the worst risk to my health is a headache from flakey libraries. This sounds like a terrifying job!

Re: France issues moratorium on prion research after fatal brain disease strikes

#240
post #79

Earlier quoted context omitted.

“ vCJD or “classic” CJD, which is not known to be caused by prions from animals. Classic CJD strikes an estimated one person per million. Some 80% of cases are sporadic, meaning they have no known cause, ” Who knows really. 10 years is a long time to wait and worry, but it can take up to 50 years to express itself. Just imagine spending your whole life worrying about this.

https://en.m.wikipedia.org/wiki/Bovine_spongiform_encephalop... Wikipedia thinks otherwise. The whole UK population was eating mad cow for years until humans started dying. It was well known in advance that this was a crazy callous risk taken by uk.gov Careful what you read, the UK spend a lot of money on propaganda at the time (to support beef exports) until the case was well and truly lost.

Bear in mind that eating muscle tissue from infected animals is a much lower risk than innoculating yourself directly with brain matter from an infected animal.

The prion protein is expressed in the central nervous system, which isn't legal for human consumption. Also, ingestion of meat exposes it to stomach acid and digestive enzymes before it gets into the consumer's circulation -- enzymes that break down foreign proteins into (harmless) amino acids.

In contrast, accidentally injecting yourself with material from an infected brain is about the most direct possible infection route.

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