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Artificial Prion Created
jabberjaw writes "Nature is reporting that researchers at the University of California San Diego have created a synthetic prion which, when injected into mice will bring about symptoms similar to those displayed by cattle suffering from bovine spongiform encephalopathy, aka mad cow disease. The researchers first crafted healthy prion proteins using bacteria. They then shook these proteins until they resembled the tangled structure of an unhealthy prion. Afterwords, these prions were injected into the brains of mice who fell ill two years later. Perhaps someone who is more familiar with this field of research would care to fill us in on the details as the article was rather light."
We gave mice mad cow disease! Yay!
:)
This is the first step, I'm sure, to giving it to politicians.
On perhaps a bit more serious of a note, what does this do for us? Is this highlighting that we now know HOW the disease is created, so we can start developing a cure? Or am I wrong. Again.
Mod me down with all of your hatred and your journey towards the dark side will be complete!
Don't eat the beef that comes from those experimental mice.
they should get an award just for keeping mice alive for two years. When I was a kid my pet mice lasted like two months and I kept good care of them too. I'm not as interested in the mad cow/mice disease as I am in the mouse longevity.
because prions are more basic and fundamental than even germs/viruses. most modern methods of treating diseases and fighting virus involve disrupting the replication process of the virus/germs, usually by the means of inhibiting certain proteins. however prions themselves are malformed proteins that malform other good proteins. this mechanism is quite hard to stop because it is so simple, there is no complicated repoduction chain to disrupt like a virus. there is only one way to stop this chain, which is to basically burn the protein to a crisp.
They couldn't fix my brakes, so they made my horn louder.
I've not read the article.. but a little synopse of how BSE works... Everyone already has the protein for BSE in their brain. Except in its natural form in the brain.. its meta-table.. Meaning it can unfold and refold into its original shape. The interesting thing about BSE is its super-stable fold of the protein. What makes this dangerous is proteins can learn new and unique ways of folding.. so if in contact with a BSE protein it'll learn to fold the BSE way. Meaning.. it'll learn to fold superstable.. which is basically a knot you can't untie. Proteins are the messengers of the body.. and if they can't unfold to be read.. its basically dead weight. After a couple years too many proteins have been retrained, leading to loss of cognitive abilities.. tada... your cow has the mad shakes!
is that we have more of a problem then previously realized. Here in colorado, we are heavily infected with Chronic wasting disease in our elk and deer. The first problem is that these deer/elk are intermingling with cattle to obtain water and grain (we are in a severe drought). About 3 year ago (pre 9/11), the state went after funding to research more of CWD/MCD/CJD/Scappies/etc. The GWB admin shot it down and then last year allocated the same program at UT to research the problem here. Amazing.
I prefer the "u" in honour as it seems to be missing these days.
"Those representing the U.S. meat industry say the U.S. government's testing program is more than adequate."
-CNN
One more reason to stop eating meat
The abstract for the original Science article is here. However, you need to register(free to see abstracts) first. You can also pay to see the fulltext.
X-Has-Sig: yes
I know people have been struggling to show that a synthetic prion can cause a disease, thereby proving beyond any doubt that it really is the prion protein (no virus, no bacterium) that causes the disease, and this may be the proof. But at 2 years of age mice are usually about to die, so this doesn't seem that convincing... It will depend on the details. Btw., there is a lot of other evidence that prions cause the mad cow disease and the human variant Creutzfeld-Jakob's disease, but if this report is true, that really nails it. Another btw.: the original paper was published in Science, Nature only refers to the Science article.
This was done at UCSF, not UCSD. Read the article
There are still a few people the dis-believe the prion theory of disease put forward by Pruisner. For those who aren't familiar with the subject, prions are essentially misfolded proteins that can induce their mis-folding by interacting with copies of themselves. So, if protein A become randomly misfolded into A', it can bump into other copies of A and induce them to form A'. In many of the disease cases, these misfolded proteins can form plaques or tangles which then disrupt or rupture and kill cells.
While Pruisner's evidence for such a mechanism is more or less overwhelming there were still a couple people who didn't buy the story. The experiment talked about here (and I haven't seen the actual paper yet, but look forward to reading it) is rather difficult to do and is pretty much the last nail in the coffin of those disagreeing with prion theory. They do complain that the protein activities of the mutants were really low and that the mice used were not of the ideal strain buut this is missing the forest through the trees. As far as all of us whose opinions matter are concerned, the case is no more than closed and the pro-Pruisner side has won.
BTW, I've heard Pruisner say that a lot of neurological diseases are really prion based...but that case is far from being closed...so keep your ears open for such discussions in the future.
-Devon (who should disclose that he's a neuro grad student at UCSF, but works on neurogenetic diseases and not prions)
Yes, I am a microbiologist, and I've done research on prions.
Basically, prions are proteins which are able to act upon other proteins and thereby create functional copies of themselves (identical copies are not needed). BSE (mad cow disease) and CJD (essentially the human version) are caused by 'rogue' prions which destroy tissue by converting large quantities of protein into more prions. Prions are basically the most elementary form of an infectious disease (as they are simply protein, no genetic material required).
Now, what these researchers have done is to prove that prions can spontaneously develop, without the need for viral or bacterial infection. Random changes in protein structure MAY result in prion creation. You needn't eat some mad cow (nor cannibalize some CJD gray matter) to contract CJD or some other prion-induced malady. Nor is a viral/bacterial infection required; the disease may develop spontaneously.
Hopefully this makes sense... I've had a few too many Schooners (beer).
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Great, now we have yet another form of weapon of mass destruction.
Artificial prions are chemical weapons, just like VX, sarin, and other nerve agents. Unlike nuclear weapons, chemical weapons are technically not weapons of mass destruction because only a nuclear reaction can destroy mass.
The analogy I like to use is that prions are the protein version of "The Living Dead". One zombie protein will convert any healthy proteins it comes into contact with, those newly created zombie proteins will convert other ones, etc., until there aren't any healthy proteins left. It doesn't hurt that the analogy involves brains...
The way in which a prion can influence a protein to mis-fold and become a prion is oddly reminiscent of the way an Ice-Nine molecule could make ordinary water molecules crystallize into a form which was solid at room temperature. To clarify: Ice-Nine was a fictional concept described in Kurt Vonnegut's novel "Cats Cradle." I wonder if it could have had any influence in real science, as opped to science fiction.
The guy in charge of the project wasn't interested in pursuing the results because the intersection of protein dynamics and hydrodynamics wasn't somewhere he wanted to go.
It will be interesting to see if they can develop anything more than handwaving explanations for how the shaking is causing the prions to change structure. Standard molecular dynamics simulations of proteins don't model mixing behavior of the water molecules surrounding the protein. Part of this may be due to the different time scales of the two phenomena.
As has been hinted at in other entries here, a prion is an alternate, stable, but nonworking and here's the kicker *infectious* conformation of a normal brain protein.
Proteins fold and twist, combine, etc., into little functional specially-shaped nuggets, sheets, strands, etc. What's strangely intuitive about functional proteins is how many of them function based on their shape. No obscure chemsistry or quantum effects here; they make little socket wrenches, funnels, motors, lock-and-key assemblies, etc.
However, that's not to say that because their core function doesn't have to do with their electronic properties, that these aren't important. Since their individual atoms do still have charge effects, they can be deformed, ("denatured",) reshaped, etc. They can also do this to each other. E.g. certain enzymes have two "sockets": the one that would normally work on a target molecule is bent out of shape and inactive until some other "cofactor" atom or molecule snicks into the back of the enzyme, bending it differently and opening up the active area.
So proteins are a little flexible, and can affect each other's shapes if they're close enough. As previously mentioned, the kicker: you can take certain sheet-like molecules in the brain and mutate them so that not only do they no longer work right, but they generate a charge field around themselves that will eff up other, similar molecules that encounter them, *and so on*
So you end up with this Night of Living Dead effect where as soon as you make a legit molecule of this kind, it goes off all peppily into the brain, doing its deal, until it encounters a zombie prion, and hey, you don't look right...but...somehow..seductive...yes! I will join you in your plaque pile! I must tell others! So you get scrapie or CWD or mad cow or some others.
What I have always thought strange is that no one seems to have looked at prions as a possible cause of Alzheimers', another poorly-understood neurological disease marked by pileups of nonfunctional protein plaques in the brain.
The reason this is significant? Folks, I thought this was one of your core beliefs! The only way to really truly understand something complex (a cake, a compiler, a neuropathic protein) is to build one that works.
There's no reason to suspect the involvement of the Soviet (or any other) bioweapons program. The prion disease scrapie has existed in sheep for many decades (see www.ag.state.co.us/animals/livestock_disease/scrap ie.html), and is presumed to be the source of the infection that started the mad cow epidemic.
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And even before BSE, it was known through the work of Carleton Gajdusek and others (www.nobel.se/medicine/laureates/1976/gajdusek-le
that the prion disease kuru in humans could be transmitted by eating infected tissue.
So it's all natural, in a sense. Which doesn't make it any less scary.
Kluge
That being said, in this prion story, we have an some example of postulates 2-4. The Prusiner team synthesized an artificial agent that's implicated in disease, and used it to infect and create new diseased organisms. This is a scientific step forward. Previously, the prion agent itself correlative with disease, but as to whether it is the causative agent, it was unclear.
The brief criticisms in the NY Times articles may have some merit though. It's still possible that the disease has some other underlying cause, and the artificial prion only hastened onset. This is an important point, because the signs of aggregate prions (the amyloid plaques) are found in BOTH healthy and diseased animals, thereby violating the first Koch postulate in some sense. However, I warn the reader that my knowledge is deficient here. Perhaps the amyloid plaques are composed of misfolded variants of other proteins also.
This is a rough summary of what I know. I hope I haven't offended any experts who know the details. Please feel free to correct what I'm sure are numerous mistakes.
Somewhere else in thread, someone asks if this is a first step to a cure. Not wanting to sound alarmist, but I will anyway.
Suppose some not-so-nice people find a way to medicate the symptoms away(needing injections/pills/treatments) to make you functional, do you think they(he-who-would-profit) would create a cure? Look at diabetes. Nasty. If there was money in a cure, nobody would need insulin shots. Truth is, cutting down on sugar intake is a better preventative.
This(BSE) however, is insidious. It takes years to manifest, and by that time, you could be done for. Another worst case-if you have a treatment for the condition, if you displease someone who wants you gone, all it takes is for them to MAKE the prion fold wrong(tampering with the treatment to cause it) instead of mitigate the bad folded ones, you would be none the wiser, and it wouldn't show for years. Not saying that Pharmas have ethical problems...*cough*
I see it as a tool, and how this tool will be used will determine what the outcome is.
And a short blurb about Alzheimers. It appears some of the people diagnosed with it actually have CJD(human equivalent). I'll leave it up to newsies/linker types to Google it.
Oh, FYI-the prion 'dies' at around 1000 C. You'd kill any patient you try to 'clean'. Perhaps it resonates at a different frequency than the normal folded sequence. Detection(absorption) and irradication(more power) might be possible.
Yeah, it creeps me way out. Appologies for bad grammar, spelling-it's late. Sweet dreams...
This mind intentionally left blank.
The KKK a bunch of sheetheads? You decide!
Maybe if we'd consider the crazy idea that in nature, herbivores don't eat other herbivores, but when fed a regular diet made up of their friends and family, weird shit might happen?
One more reason to stop eating meat
If you want to avoid food that contains beef by-products, you'll need to stop eating more than just meat. For example, most cheese is made with animal-based rennet. Its source is the stomach linings of mammals like cows.
"...always new atoms but always doing the same dance, remembering what the dance was yesterday." -Richard Feynman
What makes this dangerous is proteins can learn new and unique ways of folding.. so if in contact with a BSE protein it'll learn to fold the BSE way. Meaning.. it'll learn to fold superstable.. which is basically a knot you can't untie. Proteins are the messengers of the body.. and if they can't unfold to be read.. its basically dead weight.
I'm not sure what you think you mean by "messengers of the body", but proteins are not information storage devices. They are products of genes, which are encoded by DNA, which is the information-carrying molecule of living organisms.
Proteins are functional or structural objects -- they act as scaffolding, motors and chemical reaction centers. They can be modified in ways that allow the transmission of information (e.g. phosphorylation), but that's a secondary responsibility.
That said, your description of BSE is incorrect. Proteins are not unfolded for "reading." They fold to assume their functional shape, and unfolding destroys their function. It's not something that happens to healthy, useful proteins. In fact, the cell has mechanisms to hunt down and destroy unfolded proteins, lest they do some sort of damage.
BSE is the result of a rarity in the protein universe -- a protein that has two stable folds. Most proteins have only a single, naturally stable conformation, but the protein responsible for BSE has another. What's more, this oddball protein fold can actually catalyze the folding of other proteins into it's own shape, thus destroying their previous function. What ultimately causes the disease, however, is the propensity of these misfolded proteins to aggregate, forming solid clumps that kill the cells in which they accumulate.
BSE has nothing to do with proteins "learning" of new ways to fold. Proteins don't learn. Proteins fold correctly, or they don't -- and in this case, failing to fold correctly has a nasty consequence.
Let's try not to let fact interfere with our speculation here, OK?
Actually, prions are more like reality television. Normally, you have regular functioning TV shows being produced constantly by your big networks. However, the introduction of reality TV is dangerous because, due to its very low cost of production (you don't have to pay your actors anymore, since they are now "contestants"), it starts changing every other show on TV into a reality TV show. Over time, these reality shows aggregate throughout prime-time until eventually you have nothing but a hideous brain-destroying mass of crap.
For those of you who don't study biochemistry, here is some background information regarding the importance of this discovery:
For starters, an enzyme is a protein which specializes in catalyzing a specific reaction (lowering the amount of energy input needed to allow a reaction to occur). Proteins/enzymes are synthesized from DNA/RNA templates. The synthesis occurs in a linear fashion producing a long chain of amino acids which will eventually fold to become the protein/enzyme. The structure is classified according to proximity (primary, secondary, tertiary, quaternary). The primary structure is the amino acid sequence. Secondary structure is folding that occurs over short distances due mostly to polar attractions; this includes alpha helices and beta barrels. Tertiary structure is more of the overall shape that results forming a subunit. Quaternary stucture is the association of the subunits to create the overall protein/enzyme. Hemoglobin, for example, consists of 2 alpha subunits and 2 beta subunits around a heme (iron) core to create the complete enzyme.
The interesting thing about prions is that they are not malformed proteins due to a mutation in the primary structure as is seen in most diseases (sickle cell anemia, cancer). A prion has the exact same amino acid sequence as its healthy and properly formed counterpart; the prion simply folded in the incorrect way. When amino acid sequences are processed through molecular modelling programs to determine their final 3D conformation, often times there are multiple conformations which are thermodynamically equivalent.
When a prion is present it causes enzymes with the same primary structure within proximity to adapt its misfolded shape, thus spreading itself. The concept is similar to "ice nine" that Kurt Vonnegut Jr. describes in "Cat's Cradle" where a single crystal of ice nine is the seed which causes all other water molecules to crystalize into ice.
The significance of artificially creating a prion is that medicine may one day be able to create prions to correct enzymatic problems rather than create them. This could lead to a cure for vCJD/BSE and other undiagnosed disorders due to prions (although I do not know if it could ever correct primary structure mutations such as sickle cell anemia).
Matt
The same thing was known in kanabalistic tribes, if you eat to many brains, you go crazy.
Those prions are nothing special, they have always been there, but not in enough quantity to do any (as far as we know) harm. Those species at the end of the food chain receive some more prions through their diet, but still not in hazardess quantities.
When we started feeding cows to cows(yes, money makes prople do strange things), we created a loop in the food chain, in effect stretching the food chain infinitly. The species in the loop (cows) and those at the end of the food chain developed a new disease because of the overdose of prions.
Well, your line of thinking isn't all that unsound. But here's what we do know:
1. Prions do exist, and do infect the nervous tissue of cows (and a lot of other animals, actually.)
2. Prions are rarely (if ever) able to be found outside of the nervous tissues.
3. Consuming infected nervous tissue does appear (quite strongly, in fact) to infect the consumer.
So, our classical line of thinking about digestion and protein absorbtion doesn't quite fit what we're seeing. What does that mean, class? That's right, we'll have to keep researching both what's really going on with the digestion (or lack thereof) of prions, and the absorbtion/transmission.
Note that while BSE doesn't appeaar to be transmissible in cattle without the cannibalistic ingestion that results from human intervention, there are other related prion diseases such as CWD and scrapie that do appear to be transmitted through environmental factors. In fact, in scrapie epidemics, it has been shown that scrapie agents may remain in the local environment for years after the outbreak.
steve
Oh, you're not stuck, you're just unable to let go of the onion rings.
A lot of people have heard of "Mad Cow". Some of them have even heard of BSE or CFD. And most people don't realize that this is nothing novel, nothing new, and not at all limitted to cows.
The result of these prions in the brain is spongiform encephaly - literally, holes being eaten in your brain by the prion's interaction. Not a very fun thing!
Now, prion-caused sponfigorm encephalies have been found in a good number of animals. At a minimum, humans, goats, sheep, cows, squirrels, deer, elk, etc..
In cows, the condition is called "BSE" ("Bovine Spongiform Encephaly"). In humans, it's usually called Creutzfelt-Jacob's Disease (I'm sure I murdered the spelling). Those are merely terms for the resultant condition from the prion infection.
Now, the prion responsible for BSE isn't all that bad, as far as infectious prions go. First, it's not really transmissible in cows without the direct ingestion of infected nervous tissue. That means that if we just didn't feed cows ground up cows or ground up sheep, a very large part of the problem is solved.
However, there are other prion agents that are a bit nastier. In the case of CWD and scrapie, the prions have been shown to be transmissible to other individuals through the environment if (a) a n infected carcass or (b) excreta from an infected animal is in the area. Even better, even after all of the animals have left the area, CWD and scrapie agents have been shown to remain and still be contagious to other individuals years later.
Here's the good part: Researchers have already found genes that cause resistance to prion infections, or at least to certain types of them. The genes are found most commonly (and most heavily) in populations that practiced (or still practice) cannibalism. On the down side, it's not something as nice as getting infected and developping an immunity - we're talking about the cannibalistic societies being mostly wiped out by prion-based diseases, leaving only those (luckily) able to resist as the sole survivors, to pass along the genes to their offspring.
steve
Oh, you're not stuck, you're just unable to let go of the onion rings.
-Flesh of creature A, including malformed protein, is consumed by creature B. (Consumption is apparently part of the mechanism of infection.)
-Malformed protein avoids chemical breakdown in digestive system. This is quite possible as prions are acid and protease resistant.
-Malformed protein is taken up by Peyer's patches, sites of lymphoid tissue in the intestinal lining (Heppner, et al. in Nature Medicine, Transepithelial prion transport by M cells.) These patches normally "sample" substances from the intestinal lumen, and are instrumental in triggering an immune response if you eat something you shouldn't.
-However, your immune system doesn't find the malformed protein too threatening, possibly because it mistakes it for the very similar properly folded protein hanging out on GPI anchors all over your body's neurons. If it were recognized as dangerous, the usual method of dealing with a misfolded protein, degradation in a lysosome, wouldn't work, once again on account of prions being highly resistant to the sort of enviroment that disintegrates most proteins.
-The misfolded protein is taken up by the vagus nerve, which ennervates the gut (and does many other important things). Now, the vagus nerve may be familiar to some of you as the Tenth Cranial Nerve. So the prion rides up the long axons of the vagus to the brain.
-The prion gets to the brain, bad stuff happens and you die in a horrible manner.
Now, I can't completely assure you this is the mechanism by which prion uptake occurs, it is currently the Best Idea We Have, and I think there is evidence that it certainly could happen this way, though no guarantee that it actually does. I just wanted to mention that the gut isn't exactly an impenetrable barrier for antigens, and that it's quite possible for stuff you eat to make its way to the brain surprisingly intact. Also, how exactly do you believe the South Fore and those Britons contracted spongiform encephalopathy? They didn't stick syringes of brain matter into their heads, you know. Even a "slow virus" theory of TSE would have to take oral transmissibility into account. The studies of the Fore, for instance, note that only those who took part in funeral feasts, and then only those who ate certain parts, contracted kuru. When the feasts ended, so did the disease. Likewise, the bans and herd destructions were accompanied by a sharp dropoff in vCJD cases.
I understand that correlation does not imply causation, but I see tremendous circumstantial evidence that something these people orally ingested gave them a TSE- I mean, the natural rate for CJD is about one in a million, and then there was this sudden outbreak among people half the usual age for victims, whose only commonality was the consumption of beef, beef from cows which had consumed sheep offal...- and this experiment offers highly suggestive evidence that the agent in question was a prion.
"FDA staff reviewers expressed concern about the number of patients who were left out of the study because they died."
One more thing that you've missed is that the variant that does appear very strongly to be transmitted through the consumption of cows is not the classical CJD, but a new variant called (uninterestingly) vCJD.
The new variant occurs at a MUCH higher rate than normal CJD, and strikes much younger people. The median age for CJD is around 68, the median age for vCJD is around 28.
Furthermore, of all diagnosed vCJD to date, virtually all of had multi-year expose in Britain during the peak of the BSE epidemic.
There has never been a single vCJD case in a country where cows did not have BSE.
It's not like there's one single prion disease. There are a lot of them. And what's more, even within one prion disease, there are many different variants. Within scrapie alone, there are at least 15 different variations.
vCJD is a little worrisome in that it does appear (very strongly!) to jump from cattle to humans. On the other hand, it appears to require direct consumption of the infected animal. Stop eating beef, problem completely solved.
steve
Oh, you're not stuck, you're just unable to let go of the onion rings.
Wasn't feeling like /. without some idiotic conspiracy theory. And hey, look, it's the old favourite: those evil pharma corporations are all refusing to develop a cure.
Never mind that:
1. There _is_ money in a cure. If you had a cure for, say, Cancer and a 20 year patent on it, you could sell it for any sky-high amount of money you'd want to. It's the perfect extortion scheme. You pay up or you die a slow painful death.
2. Lo and behold, they did make cures and vaccines for a metric buttload of diseases.
3. Most importantly: there are doctors, pharmacists, managers at pharmaceuticals corporations, etc, who die of Cancer every year. Or have a bad case of diabetes. Or whose _child_ is dying of some disease.
Now you're telling me no less than they'll rather patiently wait for their own death -- or the death of those they love -- rather than break the conspiracy oath and divulge the cure. Doesn't that strike you as a completely retarded idea? If _you_ could make a cure, and you'll _die_ if you don't, wouldn't you just make the stupid cure already?
4. We're talking millions of doctors, pharmacists and researchers world wide. Some in countries where they don't even have private enterprise as you know it. (E.g., until recently the USSR and to some extent still China.) Or where it's not even easy to keep in touch with a western conspiracy. (E.g., the USSR block was pretty much isolated and guarded by a paranoid secret police.) And which invested hundreds of billions in researchs. (E.g., in developping their own nuclear weapons, sattellites, chemical weapons, biological weapons, ICBMs, etc.)
Yet you'd want me to believe that _all_ those are part of the same global conspiracy to keep some diseases untreated.
You know what? There's a medical name for that. It's called "Paranoia".
A polar bear is a cartesian bear after a coordinate transform.
Anyway, while these results from Prusiner and colleagues go a long way toward demonstrating the infectivity of prions, there are still some problems with the experiment before one can conclude that Koch's postulates have been satisfied.
I've listed some of the problems (potential and real) with the experiment here:
BTW, my scientific background is not in prions. I direct a lab that works on Epstein-Barr virus.
The only reason I clicked through to the comments is because I thought the headline said, "Artificial Pron Created"
...are an idiot.
Current research believes that 50% or more of Alzheimers patients are really a form of prion degredation of the brain. It has nothing to do with politics. It is not most common in cattle, it is most seen sheep. And the entire US herd has zero cases of BSE (Bovine Spongiform Encephalopathy). Canada has had 1, and one is unconfirmed. This however is trival. BSE is already in the food supply, of this there is no doubt. Current testing ability cannot find BSE in low levels. The only question is - are you at risk? I dunno, but -
Eat all the beef you want to, I only hope that you don't get an infected cow. A Neurosurgeon I heard speak(who has treated CJD personally) said it is the worst way to die he has ever seen - this from a guy that sees brain damage every day.
Sera
Slashdot, where armchair scientists get shouted down and armchair theologians get modded up.
>> You know what? There's a medical name for that. It's called "Paranoia".
;p
There are treatments for paranoia, but I know the world government is keeping the best of them hidden from us...
It doesn't hurt to be nice.
There are technical hurdles to using mouse models to study prion diseases. Ideally a researcher would take a completely healthy mouse and induce a prion disease with the administration of a misfolded protein. Unfortunately for researchers most healthy mice don't have a lifespan long enough to develop a prion disease from scratch. The best that the researchers are able to do is take a transgenic strain of mice (Tg196), which are known to have a DNA defect which leads to prion related disease, and administer additional amounts of the prion in order to antagonize the disease state.
/. who can answer it. The authors of the article note that Tg196 mice exhibit spontaneous disease in 30% of their population at ~550 d. The status of the control group is fairly glossed with only a single line which meantions that, as of 670 d, the control mice were still healthy. If that means _all_ the control mice why is there a deviation from the known standard? If that means _some_ of the control mice why did the peer reviewers not ask about it?
/. headline reads "Artificial prion created". That's true. The researchers brewed a batch of MoPrP(89-230) which is a truncated form of the natu
The researchers in this case leave too many questions unanswered that could have been easily addressed.
1>
The Tg196 transgenic mice express a low level of MoPrP(P101L) which is said to cause the CNS dysfunction. The researchers brew E. coli to produce a large amount of MoPrP(89-230) which they will use to spike the mice. To ensure that the additional disease effects are really attributable to the E. coli produced MoPrP(89-230), why do they not use a control group of mice which receive an extract from an E. coli broth which does _not_ produce MoPrP(89-230)?
2>
I keep pointing this out and apparently there aren't enough scientists on
3>
The bottom line worry is that a prion disease in your cow or sheep will end up in your supermarket and cause a mass plague in humans. The researchers in this study did administer Sc237 (sheep scrapie prion) to some of their mice and saw no ill effects. Paranoid people and others with a political agenda need to give up on the hype.
4>
The results are statistically fuzzy. While the authors note that 30% of a population of Tg196 mice are known to be dysfunctional at ~550 days they don't have any expected dysfunctional population % for 670 days. Their own experimental groups have a range of 380-600 and 500-670 d for unseeded and seeded groups, respectively. Additionally, at the 550 d point, both experimental groups were exhibiting about 60% CNS dysfunction in the population. The researchers have shown that administering a prion, for which the mice are known to be susceptible, will hasten their illness. It may be a good bit of lab work but it's not a surprise.
5>
The immunoblots are pretty but don't say much. The control group lacks many of the spots that the test groups have, but even the experimental group which received nothing more than the extraction/folding broth (PBS? PBH? I left the PDF on my desk) shows some of the additional bands present in the animals which received actual prions. Additionally there's the RML group. I couldn't find the definition for RML in the paper but noticed that the RML group exhibited 100% population CNS dysfunction by about 180 days. Is this really a prion effect if "RML" is more effective than the prions? Finally, where are the immunoblots for the Sc237 subjects? Ideally they would look like the control group immunoblots since the Sc237 subjects did not exhibit CNS dysfunction. My better sense tells me that the immunoblots for the Sc237 subjects would look more like the mice that received the blank extraction/folding buffer or even closer to the 9949. This would raise some obvious questions about the specificity of the immunoblot for active, MoPrP and inactive PrP from another species. This ties in with <3>.
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The
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